319 results on '"Interleukin-17 receptor"'
Search Results
2. Genetic association between interleukin-17 and susceptibility to rheumatoid arthritis
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Rong Zhao, Yi-wen Zhang, Jia-yuan Yao, Jun Qiao, Shan Song, Sheng-xiao Zhang, Cai-hong Wang, and Xiao-feng Li
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Rheumatoid arthritis ,Interleukin-17 ,Interleukin-17 receptor ,Mendelian randomization ,Genome-wide association study ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background The pathogenesis of rheumatoid arthritis (RA) is an immune imbalance, in which various inflammatory immune cells and pro-inflammatory factors are involved. Interleukin-17 (IL-17), a potent pro-inflammatory cytokine, has been found to have increased expression in the joints of patients with RA compared to healthy individuals. However, the causal relationship between the expression level of IL-17 or IL-17 receptor (IL-17R) and RA remained unknown. In this study, two-sample Mendelian randomization (MR) was used to investigate the causal relationship between IL-17 and RA. Methods Summary statistics for RA (14,361 RA cases and 43,923 healthy controls) and IL-17 (3,301 samples) were obtained from an available meta-analysis of published genome-wide association studies (GWAS). Relevant single nucleotide polymorphisms (SNPs) were selected by executing quality control steps from the GWAS summary results. Then we used bi-directional two-sample Mendelian randomization (MR) and multi-variable MR (MVMR) analysis to examine evidence of causality. MR and MVMR analyses progressed mainly using inverse variance weighted (IVW), weighted median (WM), and MR-Egger regression methods, which were applied to the genetic instrumental variables (IVs) of IL-17A/IL-17 RA, IL-17C/IL-17 RC, and IL-17D/IL-17RD and RA. For assessing the robustness of the results, we also carried out a sensitivity analysis to assess heterogeneity and pleiotropy, such as MR-Egger, leave-one-out, and MR pleiotropy residual sum and outlier (MR-PRESSO). Results Two-sample MR Analysis showed the causal relationship between IL-17A/IL-17RA and RA. The presence of genetically high IL-17A/IL-17RA may increase the risk of RA (IL-17A(OR = 1.095; 95% C.I., 0.990-1.210, p.adj = 0.013), IL-17RA(OR = 1.113, 95%CI = 1.006-1.231, p.adj = 0.006)). However, the results indicated that IL-17C/IL-17RC, and IL-17D/IL-17RD demonstrated no causal impact on RA (IL-17C(OR = 1.007, 95%CI = 0.890-1.139, p.adj = 0.152), IL-17RC(OR = 1.006, 95%CI = 0.904-1.119, p.adj = 0.152), IL-17D(OR = 0.979, 95%CI = 0.843-1.137, p.adj = 0.130), IL-17RD(OR = 0.983, 95%CI = 0.876-1.104, p.adj = 0.129)). Furthermore, MVMR analysis shown that IL-17RA(OR = 1.049, 95% CI: 0.997-1.102, p.adj = 0.014) was associated with increased risk of RA. Sensitivity analysis showed no heterogeneity and pleiotropy, suggesting that the above results were robust and reliable. Conclusion The MR analysis provides evidence that IL-17A/IL-17RA are risk factors for RA. This emphasizes the importance of intervention on IL-17A/IL-17RA in patients with RA. Developing drugs that limit IL-17A may reduce the risk of RA.
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- 2023
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3. Genetic association between interleukin-17 and susceptibility to rheumatoid arthritis.
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Zhao, Rong, Zhang, Yi-wen, Yao, Jia-yuan, Qiao, Jun, Song, Shan, Zhang, Sheng-xiao, Wang, Cai-hong, and Li, Xiao-feng
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INTERLEUKIN-17 , *GENOME-wide association studies , *SINGLE nucleotide polymorphisms , *RHEUMATOID arthritis - Abstract
Background: The pathogenesis of rheumatoid arthritis (RA) is an immune imbalance, in which various inflammatory immune cells and pro-inflammatory factors are involved. Interleukin-17 (IL-17), a potent pro-inflammatory cytokine, has been found to have increased expression in the joints of patients with RA compared to healthy individuals. However, the causal relationship between the expression level of IL-17 or IL-17 receptor (IL-17R) and RA remained unknown. In this study, two-sample Mendelian randomization (MR) was used to investigate the causal relationship between IL-17 and RA. Methods: Summary statistics for RA (14,361 RA cases and 43,923 healthy controls) and IL-17 (3,301 samples) were obtained from an available meta-analysis of published genome-wide association studies (GWAS). Relevant single nucleotide polymorphisms (SNPs) were selected by executing quality control steps from the GWAS summary results. Then we used bi-directional two-sample Mendelian randomization (MR) and multi-variable MR (MVMR) analysis to examine evidence of causality. MR and MVMR analyses progressed mainly using inverse variance weighted (IVW), weighted median (WM), and MR-Egger regression methods, which were applied to the genetic instrumental variables (IVs) of IL-17A/IL-17 RA, IL-17C/IL-17 RC, and IL-17D/IL-17RD and RA. For assessing the robustness of the results, we also carried out a sensitivity analysis to assess heterogeneity and pleiotropy, such as MR-Egger, leave-one-out, and MR pleiotropy residual sum and outlier (MR-PRESSO). Results: Two-sample MR Analysis showed the causal relationship between IL-17A/IL-17RA and RA. The presence of genetically high IL-17A/IL-17RA may increase the risk of RA (IL-17A(OR = 1.095; 95% C.I., 0.990-1.210, p.adj = 0.013), IL-17RA(OR = 1.113, 95%CI = 1.006-1.231, p.adj = 0.006)). However, the results indicated that IL-17C/IL-17RC, and IL-17D/IL-17RD demonstrated no causal impact on RA (IL-17C(OR = 1.007, 95%CI = 0.890-1.139, p.adj = 0.152), IL-17RC(OR = 1.006, 95%CI = 0.904-1.119, p.adj = 0.152), IL-17D(OR = 0.979, 95%CI = 0.843-1.137, p.adj = 0.130), IL-17RD(OR = 0.983, 95%CI = 0.876-1.104, p.adj = 0.129)). Furthermore, MVMR analysis shown that IL-17RA(OR = 1.049, 95% CI: 0.997-1.102, p.adj = 0.014) was associated with increased risk of RA. Sensitivity analysis showed no heterogeneity and pleiotropy, suggesting that the above results were robust and reliable. Conclusion: The MR analysis provides evidence that IL-17A/IL-17RA are risk factors for RA. This emphasizes the importance of intervention on IL-17A/IL-17RA in patients with RA. Developing drugs that limit IL-17A may reduce the risk of RA. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Identification of Crustacean Female Sex Hormone Receptor Involved in Sexual Differentiation of a Hermaphroditic Shrimp.
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Liu, Fang, Liu, An, and Ye, Haihui
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SEX differentiation (Embryology) , *SEX hormones , *HORMONE receptors , *CRUSTACEA , *MEMBRANE proteins - Abstract
The neurohormone crustacean female sex hormone (CFSH) contains a highly conserved interleukin-17 (IL-17) domain in the mature peptide. Although CFSH has been demonstrated to stimulate female sexual differentiation in crustaceans, its receptors (CFSHR) have been poorly reported. The present study identified an IL-17 receptor (named Lvit-IL-17R), a candidate of CFSHR, from the protandric simultaneous hermaphroditic (PSH) shrimp Lysmata vittata through GST pulldown assays and RNAi experiments. Lvit-IL-17R is a transmembrane protein with an SEFIR (similar expression as the fibroblast growth factor and IL-17R) domain, as determined through sequence analysis. A GST pulldown experiment confirmed the interactions between the type I CFSHs (CFSH1a and CFSH1b) and Lvit-IL-17R. Meanwhile, the RNAi results revealed that Lvit-IL-17R displays similar functions to type I CFSHs in regulating sexual differentiation and gonad development. In brief, Lvit-IL-17R is a potential receptor for type I CFSHs aimed at regulating the sexual differentiation of the PSH species. This study helps shed new light on the mechanism of sexual differentiation among crustaceans. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Interleukin-17 pathway inhibition with brodalumab in early systemic sclerosis: Analysis of a single-arm, open-label, phase 1 trial.
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Fukasawa, Takemichi, Yoshizaki, Ayumi, Ebata, Satoshi, Fukayama, Maiko, Kuzumi, Ai, Norimatsu, Yuta, Matsuda, Kazuki M., Kotani, Hirohito, Sumida, Hayakazu, Yoshizaki-Ogawa, Asako, Kagebayashi, Hisashi, and Sato, Shinichi
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- 2023
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6. Identification of Crustacean Female Sex Hormone Receptor Involved in Sexual Differentiation of a Hermaphroditic Shrimp
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Fang Liu, An Liu, and Haihui Ye
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crustacean female sex hormone ,interleukin-17 receptor ,protandric simultaneous hermaphroditism ,crustaceans ,sexual differentiation ,Microbiology ,QR1-502 - Abstract
The neurohormone crustacean female sex hormone (CFSH) contains a highly conserved interleukin-17 (IL-17) domain in the mature peptide. Although CFSH has been demonstrated to stimulate female sexual differentiation in crustaceans, its receptors (CFSHR) have been poorly reported. The present study identified an IL-17 receptor (named Lvit-IL-17R), a candidate of CFSHR, from the protandric simultaneous hermaphroditic (PSH) shrimp Lysmata vittata through GST pulldown assays and RNAi experiments. Lvit-IL-17R is a transmembrane protein with an SEFIR (similar expression as the fibroblast growth factor and IL-17R) domain, as determined through sequence analysis. A GST pulldown experiment confirmed the interactions between the type I CFSHs (CFSH1a and CFSH1b) and Lvit-IL-17R. Meanwhile, the RNAi results revealed that Lvit-IL-17R displays similar functions to type I CFSHs in regulating sexual differentiation and gonad development. In brief, Lvit-IL-17R is a potential receptor for type I CFSHs aimed at regulating the sexual differentiation of the PSH species. This study helps shed new light on the mechanism of sexual differentiation among crustaceans.
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- 2023
- Full Text
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7. Brodalumab to the Rescue: Efficacy and Safety of Brodalumab in Patients with Psoriasis and Prior Exposure or Inadequate Response to Biologics
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Alan Menter, April Armstrong, Abby Van Voorhees, Clive Liu, and Abby Jacobson
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Interleukin-17 receptor ,Loss of response ,Psoriasis area and severity index ,Static physician’s global assessment ,Dermatology ,RL1-803 - Abstract
Abstract While biologic therapies for psoriasis are effective for many patients, some patients may lose response, have inadequate control of disease, or develop intolerance to certain biologic agents. It may therefore be beneficial for patients whose psoriasis fails to respond to one biologic to switch to a different biologic therapy, in particular one with a different mechanism of action. However, it remains unclear how prior biologic exposure or lack of response affects the efficacy and safety of subsequent biologics in patients with moderate-to-severe psoriasis. Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, has previously been shown to be efficacious in treating moderate-to-severe psoriasis in three large phase 3 trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3). In this review, we summarize the efficacy and safety of brodalumab in patients with moderate-to-severe psoriasis and a history of biologic exposure. Further, we describe improvements in skin clearance and quality of life measures as well as safety in patients who had inadequate response to ustekinumab and who were rescued with brodalumab therapy. Lastly, we discuss improvements in skin clearance following rescue with brodalumab in patients whose disease failed to respond to secukinumab and ixekizumab. The findings of our review suggest that brodalumab is a safe and efficacious treatment regardless of past biologic use or lack of response to prior biologic therapy.
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- 2020
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8. Interleukin-17 Cytokines and Receptors: Potential Amplifiers of Tendon Inflammation
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Jolet Y. Mimpen, Sarah J. B. Snelling, Andrew J. Carr, and Stephanie G. Dakin
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tendinopathy ,interleukin-17 ,interleukin-17 receptor ,inflammation ,TNF—α ,synergy ,Biotechnology ,TP248.13-248.65 - Abstract
Interleukin (IL)-17A, a pro-inflammatory cytokine that is linked to the pathology of several inflammatory diseases, has been shown to be upregulated in early human tendinopathy and to mediate inflammatory and tissue remodelling events. However, it remains unclear which cells in tendons can respond to IL-17A, and how IL-17A, and its family members IL-17F and IL-17AF, can affect intracellular signalling activation and mRNA expression in healthy and diseased tendon-derived fibroblasts. Using well-phenotyped human tendon samples, we show that IL-17A and its receptors IL-17RA and IL-17RC are present in healthy hamstring, and tendinopathic and torn supraspinatus tendon tissue. Next, we investigated the effects of IL-17A, IL-17F, or IL-17AF on cultured patient-derived healthy and diseased tendon-derived fibroblasts. In these experiments, IL-17A treatment significantly upregulated IL6, MMP3, and PDPN mRNA expression in diseased tendon-derived fibroblasts. IL-17AF treatment induced moderate increases in these target genes, while little change was observed with IL-17F. These trends were reflected in the activation of intracellular signalling proteins p38 and NF-κB p65, which were significantly increased by IL-17A, modestly increased by IL-17AF, and not increased by IL-17F. In combination with TNF-α, all three IL-17 cytokines induced IL6 and MMP3 mRNA expression to similar levels. Therefore, this study confirms that healthy and diseased tendon-derived fibroblasts are responsive to IL-17 cytokines and that IL-17A induces the most profound intracellular signalling activation and mRNA expression of inflammatory genes, followed by IL-17AF, and finally IL-17F. The ability of IL-17 cytokines to induce a direct response and activate diverse pro-inflammatory signalling pathways through synergy with other inflammatory mediators suggests a role for IL-17 family members as amplifiers of tendon inflammation and as potential therapeutic targets in tendinopathy.
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- 2021
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9. Levels of IL-23/IL-17 Axis in Plasma and Gingival Tissue of Periodontitis Patients According to the New Classification
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Ruth Rodríguez-Montaño, Alondra del Carmen Ruiz-Gutiérrez, Vianeth María del Carmen Martínez-Rodríguez, Juan Ramón Gómez-Sandoval, Juan Manuel Guzmán-Flores, Julieta Sarai Becerra-Ruiz, Ana Lourdes Zamora-Perez, and Celia Guerrero-Velázquez
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Interleukin-23 ,Interleukin-17 ,Interleukin-23 receptor ,Interleukin-17 receptor ,periodontitis ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Background: Periodontitis (P) is a chronic inflammatory disease characterized by the destruction of periodontium support tissue generated by different immuno-inflammatory mechanisms, including the RANK/RANKL/OPG and the IL-23/IL-17 axis. Methods: The study was performed with healthy subjects (HS) and patients with periodontitis. Plasma samples were obtained from peripheral blood and the gingival tissue (GT) during periodontal surgery. The ELISA technique was used to evaluate the levels of IL-23, IL-17A, IL-23R, and IL-17RA. Results: In the plasma, a significant decrease in IL-17A was observed in patients with periodontitis than HS. In the GT, IL-23, IL-17A, and IL-17RA levels were increased in periodontitis patients; on the contrary, IL-23R levels were decreased in periodontitis patients when compared with HS. Finally, several positive correlations were found: soluble IL-17RA (sIL-17RA) levels in plasma between the percentage of radiographic bone loss (RBL%), and IL-23 with IL-17A in gingival tissue. Conclusions: The detection of the IL-23/IL-17A axis in gingival tissue and plasma provides us with more information on the behavior of this axis in a localized way in the periodontal microenvironment, in contrast to the systemic levels evaluated according to the new classification of periodontitis.
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- 2022
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10. Brodalumab to the Rescue: Efficacy and Safety of Brodalumab in Patients with Psoriasis and Prior Exposure or Inadequate Response to Biologics.
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Menter, Alan, Armstrong, April, Van Voorhees, Abby, Liu, Clive, and Jacobson, Abby
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PATIENT safety , *PSORIASIS , *BIOLOGICALS , *MONOCLONAL antibodies - Abstract
While biologic therapies for psoriasis are effective for many patients, some patients may lose response, have inadequate control of disease, or develop intolerance to certain biologic agents. It may therefore be beneficial for patients whose psoriasis fails to respond to one biologic to switch to a different biologic therapy, in particular one with a different mechanism of action. However, it remains unclear how prior biologic exposure or lack of response affects the efficacy and safety of subsequent biologics in patients with moderate-to-severe psoriasis. Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, has previously been shown to be efficacious in treating moderate-to-severe psoriasis in three large phase 3 trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3). In this review, we summarize the efficacy and safety of brodalumab in patients with moderate-to-severe psoriasis and a history of biologic exposure. Further, we describe improvements in skin clearance and quality of life measures as well as safety in patients who had inadequate response to ustekinumab and who were rescued with brodalumab therapy. Lastly, we discuss improvements in skin clearance following rescue with brodalumab in patients whose disease failed to respond to secukinumab and ixekizumab. The findings of our review suggest that brodalumab is a safe and efficacious treatment regardless of past biologic use or lack of response to prior biologic therapy. [ABSTRACT FROM AUTHOR]
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- 2020
- Full Text
- View/download PDF
11. Ferulic acid altered IL-17A/IL-17RA interaction and protected against imiquimod-induced psoriasis-like skin injury in mice.
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Lo, Hsin-Yi, Li, Chia-Cheng, Cheng, Hui-Man, Liu, I-Chen, Ho, Tin-Yun, and Hsiang, Chien-Yun
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FERULIC acid , *SKIN injuries , *MICE , *IMMUNOSTAINING , *MITOGEN-activated protein kinases , *GLOBAL analysis (Mathematics) - Abstract
Ferulic acid (FA), a phenolic phytochemical, is commonly found in grains, vegetables, and fruits. Interleukin-17A (IL-17A) and IL-17 receptor A (IL-17RA) interaction is one of important therapeutic targets for psoriasis. Here we analyzed the FA effects on IL-17A/IL-17RA interaction and psoriasis-like skin injury induced by imiquimod (IMQ). IL-17A-blocking assay and docking analysis showed that FA interacted with Trp-67, Gln-94, and Glu-95 residues of IL-17A via hydrogen bonds and consequently abolished the binding of IL-17RA to IL-17A. Mice were topically given with IMQ and orally given with various amounts of FA for 14 consecutive days. FA attenuated IMQ-induced psoriasis-like skin lesions in a dose-dependent manner, and the epidermal thickness of mice treated with 100 mg/kg FA was reduced by 53.48 ± 4.44% in comparison with sham. Global analysis of differentially expressed genes showed that IMQ and FA significantly affected immune response, metabolism, and mitogen-activated protein kinase signaling pathways. Immunohistochemical staining showed that FA inhibited the infiltration and the cytokine secretion of Th17 cell, dendritic cell, and granulocyte subsets in psoriatic skin tissues. In conclusion, we newly identified that oral administration of FA protected against IMQ-induced psoriatic skin injury in mice. Moreover, its protection was associated with the interference of IL-17A/IL-17RA interaction. Image 1 • Ferulic acid is a phenolic phytochemical that is commonly found in grains, vegetables, and fruits. • Ferulic acid protected against imiquimod-induced psoriasis-like skin injury in mice. • Ferulic acid was a novel IL-17A-targeting compound that altered the interaction between IL-17A and IL-17RA. [ABSTRACT FROM AUTHOR]
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- 2019
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12. Proteomic characterisations of ulcerative colitis endoscopic biopsies associate with clinically relevant histological measurements of disease severity
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Aaron M Gruver, Salisha Hill, Daniel C. Liebler, Jochen Schmitz, Juraj Bodo, Keith Lai, Robert J. Benschop, Bradley L. Ackermann, David C Gemperline, Ryan D. Morrison, Eric D. Hsi, and Matt D Westfall
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Proteomics ,Interleukin-23 receptor ,Pathology ,medicine.medical_specialty ,business.industry ,Biopsy ,Colonoscopy ,General Medicine ,Interleukin-17 receptor ,medicine.disease ,Interleukin-23 ,Severity of Illness Index ,Ulcerative colitis ,Pathology and Forensic Medicine ,Interleukin 23 ,Humans ,Medicine ,Colitis, Ulcerative ,Histopathology ,Interleukin 17 ,Intestinal Mucosa ,Colitis ,business ,G alpha subunit - Abstract
Aims and methodsAccurate protein measurements using formalin-fixed biopsies are needed to improve disease characterisation. This feasibility study used targeted and global mass spectrometry (MS) to interrogate a spectrum of disease severities using 19 ulcerative colitis (UC) biopsies.ResultsTargeted assays for CD8, CD19, CD132 (interleukin-2 receptor subunit gamma/common cytokine receptor gamma chain), FOXP3 (forkhead box P3) and IL17RA (interleukin 17 receptor A) were successful; however, assays for IL17A (interleukin 17A), IL23 (p19) (interleukin 23, alpha subunit p19) and IL23R (interleukin 23 receptor) did not permit target detection. Global proteome analysis (4200 total proteins) was performed to identify pathways associated with UC progression. Positive correlation was observed between histological scores indicating active colitis and neutrophil-related measurements (R2=0.42–0.72); inverse relationships were detected with cell junction targets (R2=0.49–0.71) and β-catenin (R2=0.51–0.55) attributed to crypt disruption. An exploratory accuracy assessment with Geboes Score and Robarts Histopathology Index cut-offs produced sensitivities/specificities of 72.7%/75.0% and 100.0%/81.8%, respectively.ConclusionsPathologist-guided MS assessments provide a complementary approach to histological scoring systems. Additional studies are indicated to verify the utility of this novel approach.
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- 2021
13. Interleukin‐17 family cytokines in protective immunity against infections: role of hematopoietic cell‐derived and non‐hematopoietic cell‐derived interleukin‐17s.
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Matsuzaki, Goro and Umemura, Masayuki
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CYTOKINES ,CELLULAR immunity ,HEMATOPOIETIC growth factors ,NEUTROPHILS ,PATHOGENIC microorganisms - Abstract
ABSTRACT: Interleukin‐17 family cytokines, consisting of six members, participate in immune response in infections and autoimmune and inflammatory diseases. The prototype cytokine of the family, IL‐17A, was originally identified from CD4+ T cells which are now termed Th17 cells. Later, IL‐17A‐producing cells were expanded to include various hematopoietic cells, namely CD8+ T cells (Tc17), invariant NKT cells, γδ T cells, non‐T non‐B lymphocytes (termed type 3 innate lymphoid cells) and neutrophils. Some IL‐17 family cytokines other than IL‐17A are also expressed by CD4+ T cells: IL‐17E by Th2 cells and IL‐17F by Th17 cells. IL‐17A and IL‐17F induce expression of pro‐inflammatory cytokines to induce inflammation and anti‐microbial peptides to kill pathogens, whereas IL‐17E induces allergic inflammation. However, the functions of other IL‐17 family cytokines have been unclear. Recent studies have shown that IL‐17B and IL‐17C are expressed by epithelial rather than hematopoietic cells. Interestingly, expression of IL‐17E and IL‐17F by epithelial cells has also been reported and epithelial cell‐derived IL‐17 family cytokines shown to play important roles in immune responses to infections at epithelial sites. In this review, we summarize current information on hematopoietic cell‐derived IL‐17A and non‐hematopoietic cell‐derived IL‐17B, IL‐17C, IL‐17D, IL‐17E and IL‐17F in infections and propose functional differences between these two categories of IL‐17 family cytokines. [ABSTRACT FROM AUTHOR]
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- 2018
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14. Characterization and expression analysis of six interleukin-17 receptor genes in grouper (Epinephelus coioides) after Cryptocaryon irritans infection.
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Jiang, Biao, Li, Yan-Wei, Hu, Ya-Zhou, Luo, Heng-Li, and Li, An-Xing
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GROUPERS , *FISH parasites , *FISH immunology , *INTERLEUKINS , *CELL communication , *CRYPTOCARYON irritans - Abstract
Interleukin-17 receptors (IL17Rs) mediate the activation of several downstream signal pathways to induce inflammatory response and contribute to the pathology of many autoimmune diseases. In this study, six IL17Rs (IL17RA1, RA2, RB, RC, RD and RE) were cloned and characterized from Epinephelus coioides , an orange-spotted grouper. Multiple sequence alignment and structural analysis revealed that all members of IL17Rs were low in sequence identity with each other. But their structures were conservative in grouper, which contain signal peptide, extracellular FNIII domain (IL17RA1/RA2/RB) or IL-17_R_N domain (IL17RC/RD/RE), transmembrane domain and SEFIR domain in their intracellular region. The analysis of tissue distribution showed these six genes were ubiquitously and differentially expressed in all major types of tissues. What's more, it is interesting to find their high expression in immune tissues (liver, gill, skin and thymus). IL17RA1 and IL17RA2 were significantly down-regulated at all time-points in gill and spleen after Cryptocaryon irritans infection, however, there was no significant change in other grouper IL17Rs. It suggests that the C. irritans may escape from the host immunity or the host prevents serious inflammation by inhibiting the expression of ILl7Rs. [ABSTRACT FROM AUTHOR]
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- 2017
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15. Role of Interleukin 17A in Aortic Valve Inflammation in Apolipoprotein E-deficient Mice
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Yefan Jiang, Nianguo Dong, Geng Li, Fayuan Liu, Peng Bai, and Chong Chu
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Male ,Apolipoprotein E ,Aortic valve ,medicine.medical_specialty ,Inflammation ,Interleukin-17 receptor ,Diet, High-Fat ,Biochemistry ,Mice ,Apolipoproteins E ,Downregulation and upregulation ,Internal medicine ,Databases, Genetic ,Genetics ,Animals ,Humans ,Medicine ,Cell Nucleus ,Receptors, Interleukin-17 ,business.industry ,Interleukin-17 ,NF-kappa B ,Antibodies, Monoclonal ,Aortic Valve Stenosis ,medicine.disease ,Up-Regulation ,Cellular infiltration ,Disease Models, Animal ,Protein Transport ,Endocrinology ,medicine.anatomical_structure ,Interleukin 17 ,medicine.symptom ,business ,Infiltration (medical) ,Injections, Intraperitoneal - Abstract
SummaryInterleukin 17A (IL17A) is reported to be involved in many inflammatory processes, but its role in aortic valve diseases remains unknown. We examined the role of IL17A based on an ApoE−/− mouse model with strategies as fed with high-fat diet or treated with IL17A monoclonal antibody (mAb). 12 weeks of high-fat diet feeding can elevate cytokines secretion, inflammatory cells infiltration and myofibroblastic transition of valvular interstitial cells (VICs) in aortic valve. Moreover, diet-induction accelerated interleukin 17 receptor A (IL17RA) activation in VICs. In an IL17A inhibition model, the treatment group was intra-peritoneally injected with anti-IL17A mAb while controls received irrelevant antibody. Functional blockade of IL17A markedly reduced cellular infiltration and transition in aortic valve. To investigate potential mechanisms, NF-κB was co-stained in IL17RA+ VICs and IL17RA+ macrophages, and further confirmed by Western blotting in VICs. High-fat diet could activate NF-κB nuclear translocation in IL17RA+ VICs and IL17RA+ macrophages and this process was depressed after IL17A mAb-treatment. In conclusion, high-fat diet can lead to IL17A upregulation, VICs myofibroblastic transition and inflammatory cells infiltration in the aortic value of ApoE−/− mice. Blocking IL17A with IL17A mAb can alleviate aortic valve inflammatory states.
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- 2020
16. The IL-17 receptor IL-17RE mediates polyIC-induced exacerbation of experimental allergic asthma
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Felix Ritzmann, Christoph Beisswenger, Robert Bals, Christian Herr, Lars Lunding, Michael Wegmann, Anja Honecker, and Giovanna Vella
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0301 basic medicine ,Chemokine ,Exacerbation ,Ovalbumin ,medicine.medical_treatment ,Inflammation ,Respiratory Mucosa ,Interleukin-17 receptor ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Respiratory Hypersensitivity ,medicine ,Animals ,Lung ,Asthma ,Mice, Knockout ,lcsh:RC705-779 ,Receptors, Interleukin-17 ,biology ,business.industry ,Research ,Interleukin-17 ,Pattern recognition receptor ,Epithelial Cells ,lcsh:Diseases of the respiratory system ,respiratory system ,medicine.disease ,Mice, Inbred C57BL ,Poly I-C ,030104 developmental biology ,Cytokine ,Neutrophil Infiltration ,Immunology ,biology.protein ,Cytokines ,Nasal administration ,Inflammation Mediators ,medicine.symptom ,business ,Bronchoalveolar Lavage Fluid ,030215 immunology - Abstract
BackgroundThe interleukin 17 receptor E (IL-17RE) is specific for the epithelial cytokine interleukin-17C (IL-17C). Asthma exacerbations are frequently caused by viral infections. Polyinosinic:polycytidylic acid (pIC) mimics viral infections through binding to pattern recognition receptors (e.g. TLR-3). We and others have shown that pIC induces the expression of IL-17C in airway epithelial cells. Using different mouse models, we aimed to investigate the function of IL-17RE in the development of experimental allergic asthma and acute exacerbation thereof.MethodsWild-type (WT) and IL-17RE deficient (Il-17re−/−) mice were sensitized and challenged with OVA to induce allergic airway inflammation. pIC or PBS were applied intranasally when allergic airway inflammation had been established. Pulmonary expression of inflammatory mediators, numbers of inflammatory cells, and airway hyperresponsiveness (AHR) were analyzed.ResultsAblation of IL-17RE did not affect the development of OVA-induced allergic airway inflammation and AHR. pIC induced inflammation independent of IL-17RE in the absence of allergic airway inflammation. Treatment of mice with pIC exacerbated pulmonary inflammation in sensitized and OVA-challenged mice in an IL-17RE-dependent manner. The pIC-induced expression of cytokines (e.g. keratinocyte-derived chemokine (KC), granulocyte-colony stimulating factor (G-CSF)) and recruitment of neutrophils were decreased inIl-17re−/−mice. pIC-exacerbated AHR was partially decreased inIl-17re−/−mice.ConclusionsOur results indicate that IL-17RE mediates virus-triggered exacerbations but does not have a function in the development of allergic lung disease.
- Published
- 2020
17. Brodalumab to the Rescue: Efficacy and Safety of Brodalumab in Patients with Psoriasis and Prior Exposure or Inadequate Response to Biologics
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April W. Armstrong, Alan Menter, Clive Liu, Abby S. Van Voorhees, and Abby Jacobson
- Subjects
medicine.medical_specialty ,Brodalumab ,Review ,Dermatology ,Disease ,Interleukin-17 receptor ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Psoriasis Area and Severity Index ,Psoriasis ,Ustekinumab ,Medicine ,Intensive care medicine ,Psoriasis area and severity index ,business.industry ,Static physician’s global assessment ,medicine.disease ,Ixekizumab ,RL1-803 ,030220 oncology & carcinogenesis ,Secukinumab ,Loss of response ,business ,medicine.drug - Abstract
While biologic therapies for psoriasis are effective for many patients, some patients may lose response, have inadequate control of disease, or develop intolerance to certain biologic agents. It may therefore be beneficial for patients whose psoriasis fails to respond to one biologic to switch to a different biologic therapy, in particular one with a different mechanism of action. However, it remains unclear how prior biologic exposure or lack of response affects the efficacy and safety of subsequent biologics in patients with moderate-to-severe psoriasis. Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, has previously been shown to be efficacious in treating moderate-to-severe psoriasis in three large phase 3 trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3). In this review, we summarize the efficacy and safety of brodalumab in patients with moderate-to-severe psoriasis and a history of biologic exposure. Further, we describe improvements in skin clearance and quality of life measures as well as safety in patients who had inadequate response to ustekinumab and who were rescued with brodalumab therapy. Lastly, we discuss improvements in skin clearance following rescue with brodalumab in patients whose disease failed to respond to secukinumab and ixekizumab. The findings of our review suggest that brodalumab is a safe and efficacious treatment regardless of past biologic use or lack of response to prior biologic therapy.
- Published
- 2020
18. Interleukin-17 Cytokines and Receptors: Potential Amplifiers of Tendon Inflammation
- Author
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Mimpen, JY, Snelling, SJB, Carr, AJ, and Dakin, SG
- Subjects
Histology ,interleukin-17 receptor ,inflammation ,TNF—α ,Biomedical Engineering ,Bioengineering and Biotechnology ,synergy ,Bioengineering ,tendinopathy ,TP248.13-248.65 ,Biotechnology ,Original Research ,interleukin-17 - Abstract
Interleukin (IL)-17A, a pro-inflammatory cytokine that is linked to the pathology of several inflammatory diseases, has been shown to be upregulated in early human tendinopathy and to mediate inflammatory and tissue remodelling events. However, it remains unclear which cells in tendons can respond to IL-17A, and how IL-17A, and its family members IL-17F and IL-17AF, can affect intracellular signalling activation and mRNA expression in healthy and diseased tendon-derived fibroblasts. Using well-phenotyped human tendon samples, we show that IL-17A and its receptors IL-17RA and IL-17RC are present in healthy hamstring, and tendinopathic and torn supraspinatus tendon tissue. Next, we investigated the effects of IL-17A, IL-17F, or IL-17AF on cultured patient-derived healthy and diseased tendon-derived fibroblasts. In these experiments, IL-17A treatment significantly upregulated IL6, MMP3, and PDPN mRNA expression in diseased tendon-derived fibroblasts. IL-17AF treatment induced moderate increases in these target genes, while little change was observed with IL-17F. These trends were reflected in the activation of intracellular signalling proteins p38 and NF-κB p65, which were significantly increased by IL-17A, modestly increased by IL-17AF, and not increased by IL-17F. In combination with TNF-α, all three IL-17 cytokines induced IL6 and MMP3 mRNA expression to similar levels. Therefore, this study confirms that healthy and diseased tendon-derived fibroblasts are responsive to IL-17 cytokines and that IL-17A induces the most profound intracellular signalling activation and mRNA expression of inflammatory genes, followed by IL-17AF, and finally IL-17F. The ability of IL-17 cytokines to induce a direct response and activate diverse pro-inflammatory signalling pathways through synergy with other inflammatory mediators suggests a role for IL-17 family members as amplifiers of tendon inflammation and as potential therapeutic targets in tendinopathy.
- Published
- 2021
19. Appetite Suppression and Interleukin 17 Receptor Signaling Activation of Colonic Mycobiota Dysbiosis Induced by High Temperature and High Humidity Conditions
- Author
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Yinrui Guo, Yuanfei Fu, Haiting Zhang, Lingyan Qiu, Diling Chen, Jian Wang, Hongya Guo, and Xiangxiang Zhu
- Subjects
Microbiology (medical) ,Mycobiota ,medicine.medical_specialty ,Colon ,media_common.quotation_subject ,Gut–brain axis ,Immunology ,Appetite ,Interleukin-17 receptor ,Biology ,Microbiology ,Mice ,Cellular and Infection Microbiology ,IL-17R signaling ,Internal medicine ,medicine ,Metabolome ,host appetite ,Animals ,Microbiome ,media_common ,Original Research ,Receptors, Interleukin-17 ,gut-brain axis ,Appetite Regulation ,Basidiomycota ,Temperature ,Humidity ,medicine.disease ,immunity ,QR1-502 ,Endocrinology ,Infectious Diseases ,climate change ,colonic mycobiota ,Dysbiosis ,Interleukin 17 - Abstract
It is known that the microbiome affects human physiology, emotion, disease, growth, and development. Most humans exhibit reduced appetites under high temperature and high humidity (HTHH) conditions, and HTHH environments favor fungal growth. Therefore, we hypothesized that the colonic mycobiota may affect the host’s appetite under HTHH conditions. Changes in humidity are also associated with autoimmune diseases. In the current study mice were fed in an HTHH environment (32°C ± 2°C, relative humidity 95%) maintained via an artificial climate box for 8 hours per day for 21 days. Food intake, the colonic fungal microbiome, the feces metabolome, and appetite regulators were monitored. Components of the interleukin 17 pathway were also examined. In the experimental groups food intake and body weight were reduced, and the colonic mycobiota and fecal metabolome were substantially altered compared to control groups maintained at 25°C ± 2°C and relative humidity 65%. The appetite-related proteins LEPT and POMC were upregulated in the hypothalamus (p < 0.05), and NYP gene expression was downregulated (p < 0.05). The expression levels of PYY and O-linked β-N-acetylglucosamine were altered in colonic tissues (p < 0.05), and interleukin 17 expression was upregulated in the colon. There was a strong correlation between colonic fungus and sugar metabolism. In fimo some metabolites of cholesterol, tromethamine, and cadaverine were significantly increased. There was significant elevation of the characteristic fungi Solicoccozyma aeria, and associated appetite suppression and interleukin 17 receptor signaling activation in some susceptible hosts, and disturbance of gut bacteria and fungi. The results indicate that the gut mycobiota plays an important role in the hypothalamus endocrine system with respect to appetite regulation via the gut-brain axis, and also plays an indispensable role in the stability of the gut microbiome and immunity. The mechanisms involved in these associations require extensive further studies.
- Published
- 2021
20. Expression and clinical significance of IL-17 and IL-17 receptor in ulcerative colitis.
- Author
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Zhang, Heng, Xia, Bing, Li, Jin, Zhao, Qiu, Chen, Zhi-tao, Zhou, Rui, and Wu, Jie
- Abstract
The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor (IL-17R) in intestinal mucosa tissue in patients with ulcerative colitis (UC) and con-trols, and evaluate their relationship with disease activity and explore the role of IL-17 in the patho-genesis of UC. A total of 36 Chinese UC patients and 60 healthy controls were enrolled in this study. Serum IL-17 and C-reactive protein (CRP) levels were determined by ELISA and immu-nonephelometry, respectively. The IL-17R mRNA expression levels were detected by quantitative PCR. Serum IL-17 levels were significantly elevated in UC patients as compared with those in the healthy controls ( P<0.05). Among UC patients, serum IL-17 levels were significantly increased in active phase as compared with those in inactive phase ( P<0.05), and correlated with CRP levels ( r=0.578, P<0.01). IL-17R expression levels were higher in active UC patients than in healthy con-trols ( P<0.05). It was concluded that IL-17 levels were highly expressed in UC, especially in active phase, and correlated with CRP levels in UC patients. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
21. A defective interleukin-17 receptor A1 causes weight loss and intestinal metabolism-related gene downregulation in Japanese medaka, Oryzias latipes
- Author
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Yo Okamura, Tomoya Kono, Masato Kinoshita, Jun-ichi Hikima, Hiroshi Miyanishi, and Masahiro Sakai
- Subjects
Fish Proteins ,0301 basic medicine ,Molecular biology ,Science ,Oryzias ,Immunology ,Down-Regulation ,Interleukin-17 receptor ,Article ,Animals, Genetically Modified ,Transcriptome ,Gene Knockout Techniques ,03 medical and health sciences ,0302 clinical medicine ,RAR-related orphan receptor gamma ,Weight Loss ,Animals ,Intestinal Mucosa ,Receptor ,Receptors, Interleukin-17 ,Multidisciplinary ,biology ,Wild type ,Interleukin ,Japanese Medaka ,biology.organism_classification ,Cell biology ,030104 developmental biology ,Medicine ,030215 immunology - Abstract
In the intestine, the host must be able to control the gut microbiota and efficiently absorb transiently supplied metabolites, at the risk of enormous infection. In mammals, the inflammatory cytokine interleukin (IL)-17A/F is one of the key mediators in the intestinal immune system. However, many functions of IL-17 in vertebrate intestines remain unclarified. In this study, we established a gene-knockout (KO) model of IL-17 receptor A1 (IL-17RA1, an IL-17A/F receptor) in Japanese medaka (Oryzias latipes) using genome editing technique, and the phenotypes were compared to wild type (WT) based on transcriptome analyses. Upon hatching, homozygous IL-17RA1-KO medaka mutants showed no significant morphological abnormality. However, after 4 months, significant weight decreases and reduced survival rates were observed in IL-17RA1-KO medaka. Comparison of gene-expression patterns in WT and IL-17RA1-KO medaka revealed that various metabolism- and immune-related genes were significantly down-regulated in IL-17RA1-KO medaka intestine, particularly genes related to mevalonate metabolism (mvda, acat2, hmgcs1, and hmgcra) and genes related to IL-17 signaling (such as il17c, il17a/f1, and rorc) were found to be decreased. Conversely, expression of genes related to cardiovascular system development, including fli1a, sox7, and notch1b in the anterior intestine, and that of genes related to oxidation–reduction processes including ugp2a, aoc1, and nos1 in posterior intestine was up-regulated in IL-17RA1-KO medaka. These findings show that IL-17RA regulated immune- and various metabolism-related genes in the intestine for maintaining the health of Japanese medaka.
- Published
- 2021
22. Brodalumab for the treatment of plaque psoriasis: up-to-date
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John Koo and Kristen M. Beck
- Subjects
0301 basic medicine ,medicine.drug_class ,Clinical Biochemistry ,Brodalumab ,Interleukin-17 receptor ,Antibodies, Monoclonal, Humanized ,Monoclonal antibody ,03 medical and health sciences ,0302 clinical medicine ,Psoriasis ,Drug Discovery ,Humans ,Medicine ,Receptor ,Pharmacology ,Plaque psoriasis ,Biological Products ,Clinical Trials as Topic ,Receptors, Interleukin-17 ,business.industry ,Mechanism (biology) ,Bacterial Infections ,medicine.disease ,Suicide ,Treatment Outcome ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunology ,Interleukin 17 ,business ,Half-Life - Abstract
Brodalumab is one of the most efficacious biologic agents available for psoriasis. It also has a unique mechanism; it is the only agent that blocks the entire interleukin 17 receptors instead of blocking individual cytokines. However, the main drawback is that brodalumab has an FDA mandated black box warning regarding suicide. This is an up-to-date article reviews the scientific validity of this issue with brodalumab and suicide. Areas covered: A worldwide literature search was conducted on the above issue regarding suicide risk and brodalumab. All relevant articles on this topic searchable in public domain were utilized. Expert opinion: The FDA black box warning is based on three completed suicides that happened in one research location out of 390 research sites worldwide. All three completed suicides have alternative explanations unrelated to brodalumab. The overall data from phase III clinical trials shows that psoriasis patients recorded significant improvement in depression after treatment with brodalumab. The overall impression is that the suicide issue is far from being scientifically validated and this is why the FDA itself stated in the package insert that "the cause and effect relationship these suicides and brodalumab has not been established."
- Published
- 2019
23. Interleukin‐17 receptor<scp>A</scp>blockade with brodalumab in palmoplantar pustular psoriasis: Report on four cases
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Andreas Pinter, Wiebke K. Peitsch, Rotraut Mössner, and Dagmar Wilsmann-Theis
- Subjects
Adult ,medicine.medical_specialty ,Palmoplantar pustulosis ,Brodalumab ,Dermatology ,Interleukin-17 receptor ,Antibodies, Monoclonal, Humanized ,Severity of Illness Index ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,otorhinolaryngologic diseases ,medicine ,Humans ,Psoriasis ,Adverse effect ,Aged ,Receptors, Interleukin-17 ,business.industry ,Antibodies, Monoclonal ,Interleukin ,General Medicine ,Middle Aged ,Pathophysiology ,Blockade ,Treatment Outcome ,Withholding Treatment ,030220 oncology & carcinogenesis ,Disease Progression ,Drug Therapy, Combination ,Female ,Dermatologic Agents ,business ,Mometasone Furoate ,Rare disease - Abstract
Palmoplantar pustular psoriasis, also termed palmoplantar pustulosis (PPP), is a rare disease affecting the palmoplantar regions characterized by sterile, yellow to brown pustules mostly on erythematous skin. PPP is related to a high burden due to painful, impaired and stigmatizing character. Several isoforms of interleukin (IL) have been implicated in its pathophysiology. Here, we report on four patients with PPP treated with the novel IL-17 receptor A blocker brodalumab, in whom this therapy was not successful or showed moderate improvement combined with adverse events.
- Published
- 2019
24. Interleukin-17 receptor polymorphism predisposes to primary graft dysfunction after lung transplantation.
- Author
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Somers, Jana, Ruttens, David, Verleden, Stijn E., Vandermeulen, Elly, Piloni, Davide, Wauters, Els, Lambrechts, Diether, Vos, Robin, Verleden, Geert M., Vanaudenaerde, Bart, and van Raemdonck, Dirk E.
- Subjects
- *
LUNG transplantation , *DISEASE incidence , *INTERLEUKIN-17 , *GENETIC polymorphisms , *CAUSES of death , *SURGICAL diseases , *NEUTROPHILS - Abstract
Background Primary graft dysfunction (PGD), with an incidence of 11% to 57%, is a major cause of morbidity and mortality within the first 30 days after lung transplantation (LTx). In this study, we postulate that recipient genetic variants in interleukin-17 and -23 receptor genes (IL-17R and IL-23R, respectively) may predispose LTx recipients to an increased risk for developing PGD. Methods Seven genetic variants of IL-17R and IL-23R were successfully genotyped in 431 lung transplant recipients. Our primary end-point was PGD and secondary end-points were time to extubation, intensive care unit (ICU) stay, bronchoalveolar lavage neutrophilia and serum C-reactive protein. Results The AA genotype of the rs882643 genetic variant of IL-17R was associated with higher PGD grades at 0 hour (adjusted p = 0.042), 12 hours (adjusted p = 0.013) and 48 hours (adjusted p = 0.0092) after LTx. The GG genotype of the rs2241049 genetic variant of IL-17R was associated with higher PGD grades at 48 hours (adjusted p = 0.0067) after LTx. For both genetic variants, no association was found with extubation time, ICU stay, post-operative BAL neutrophilia, serum CRP, chronic lung allograft dysfunction (CLAD) or graft loss. Conclusion Both genetic variants of IL-17R (rs882643 and rs2241049) were associated with PGD. This confirms a genetic predisposition toward PGD and suggests a role of IL-17 in driving neutrophilia in PGD. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
25. Cardiomyocyte IL-IR2 Protects Heart From Ischemia/Reperfusion Injury by Attenuating NLRP3 Inflammasome Activation and IL-17RA-Mediated Apoptosis
- Author
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Guosheng Fu, Jiacheng Wang, Jiawen Chen, Min Shang, Xue Lv, Meihui Wang, Yingchao Gong, Jun Lin, Qingbo Lv, Yanbo Zhao, and Tingting Jin
- Subjects
Programmed cell death ,business.industry ,Pyroptosis ,Ischemia ,Institutional Animal Care and Use Committee ,Inflammasome ,Interleukin-17 receptor ,Pharmacology ,medicine.disease ,Downregulation and upregulation ,medicine ,business ,Reperfusion injury ,medicine.drug - Abstract
Background: Myocardial ischemia reperfusion (I/R) is characterized by a complex inflammatory response that stimulates the formation of inflammasome and production of Interleukin-1β (IL-1β). As a decoy receptor for IL-1β, the role of Interleukin-1 receptor type 2 (IL-1R2) in myocardial I/R injury is still unclear. Here, for the first time, we report the underlying mechanisms of IL-1R2 in protecting cardiomyocyte against I/R injury. Methods: Initially, the expression of IL-1R2 in myocardial I/R injury was determined by RT-PCR and western blot assays. IL-1R2-deficiency mice and AAV-9 virus carrying IL-1R2 under cTnT promoter were administrated to identify the protective role of IL-1R2 and RNA-sequencing was performed to explore the underlying mechanisms of IL-1R2 in myocardial I/R injury. Besides, neonatal rat ventricular myocytes (NRVM) were isolated to investigate the relationships of IL-1R2, NLRP3 inflammasome and Interleukin 17 receptor A (IL-17RA). Findings: We demonstrated that the expression of IL-1R2 in cardiomyocyte was induced by I/R injury both in vivo and in vitro. IL-1R2-deficient mice decreased cardiac systolic function, increased infarct size and cardiomyocyte apoptosis. Whereas, Overexpression of IL-1R2 in cardiomyocyte protected cardiomyocyte against I/R-induced cell death through reducing the NLRP3 inflammasome activation and IL-17RA expression both in vivo and in vitro. Interpretation: Collectively, the upregulation of IL-1R2 in cardiomyocyte provides therapeutic effects in protecting cardiomyocyte against cell death during myocardial I/R injury. Funding: Natural Key Research and Development Project of Zhejiang Province, China (2018C03015), National Key Research and Development Program of China (2016YFC1102203), Zhejiang Provincial Natural Science Foundation of China under Grant (LQ17H020002). Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: The collection of blood plasma from AMI patients and healthy controls was conducted with approval from the Institutional Animal Care and Use Committee, and all animal studies were conducted with approval from the Medical Ethics Committee of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine.
- Published
- 2021
26. Interleukin-17 Receptor A1 Gene Knockout Causes Weight Loss and Reduction of Intestinal Metabolism-Related Genes in The Japanese Medaka, Oryzias Latipes
- Author
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Masato Kinoshita, Jun-ichi Hikima, Yo Okamura, Hiroshi Miyanishi, Masahiro Sakai, and Tomoya Kono
- Subjects
Weight loss ,Oryzias ,medicine ,Intestinal Metabolism ,Japanese Medaka ,Interleukin-17 receptor ,Biology ,medicine.symptom ,biology.organism_classification ,Molecular biology ,Gene ,Gene knockout - Abstract
In the intestine, the host must be able to control the gut microbiota and efficiently absorb transiently supplied metabolites, at the risk of enormous infection. In mammals, the inflammatory cytokine interleukin (IL)-17A/F is one of the key mediators in the intestinal immune system. However, many functions of IL-17 in vertebrate intestines remain unclarified. In this study, we established a gene-knockout (KO) model of IL-17 receptor A1 (RA1), an IL-17A/F receptor, in Japanese medaka (Oryzias latipes) using genome editing technique and the phenotypes were compared to wild type (WT) based on transcriptome analyses. Upon hatching, homozygous IL-17RA1-KO medaka mutants showed no significant morphological abnormality. However, after 4 months, significant weight decreases and reduced survival rates were observed in IL-17RA1-KO medaka. Comparing gene-expression patterns in WT and IL-17RA1-KO medaka revealed that various metabolism- and immune-related genes were significantly down-regulated in IL-17RA1-KO medaka intestine, particularly genes related to mevalonate metabolism (mvda, acat2, hmgcs1, and hmgcra) and genes related to IL-17 signaling (such as il17c, il17a/f1, and rorc) were found to be decreased. These findings show that IL-17RA regulated immune- and various metabolism-related genes in the intestine for maintaining the health of Japanese medaka.
- Published
- 2020
27. Conformational dynamics in interleukin 17A and 17F functional complexes is a key determinant of receptor A affinity and specificity
- Author
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Richard J. K. Taylor, Mark D. Carr, Sarah L. Strong, Alistair James Henry, Vaclav Veverka, Frederick W. Muskett, Christine E. Prosser, Alastair D. G. Lawson, Lorna C. Waters, and Neesha Dedi
- Subjects
0301 basic medicine ,Models, Molecular ,Magnetic Resonance Spectroscopy ,Protein Conformation ,Immunology ,Interleukin-17 receptor ,Crystal structure ,Biochemistry ,Proinflammatory cytokine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Amide ,Immunology and Allergy ,Humans ,Amino Acid Sequence ,Receptor ,Molecular Biology ,Receptors, Interleukin-17 ,Chemistry ,Interleukin-17 ,Hematology ,Affinities ,030104 developmental biology ,030220 oncology & carcinogenesis ,Biophysics ,Functional significance ,Interleukin 17 ,Protein Multimerization ,Protein Binding - Abstract
The proinflammatory cytokines IL-17A and IL-17F have been identified as key drivers of a range of human inflammatory diseases, such as psoriasis, which has led to several therapeutic antibodies targeted at IL-17A. The two cytokines have been shown to tightly associate as functional homo and hetero dimers, which induce signalling via the formation of a cell surface signalling complex with a single copy of both IL-17RA and IL-17RC. Striking differences in affinity have been observed for IL-17RA binding to IL-17AA, IL-17AF and IL-17FF, however, the functional significance and molecular basis for this has remained unclear. We have obtained comprehensive backbone NMR assignments for full length IL-17AA (79%), IL-17AF (93%) and IL-17FF (89%), which show that the dimers adopt almost identical backbone topologies in solution to those observed in reported crystal structures. Analysis of the line widths and intensities of assigned backbone amide NMR signals has revealed striking differences in the conformational plasticity and dynamics of IL-17AA compared to both IL-17AF and IL-17FF. Our NMR data indicate that a number of regions of IL-17AA are interconverting between at least two distinct conformations on a relatively slow timescale. Such conformational heterogeneity has previously been shown to play an important role in the formation of many high affinity protein-protein complexes. The locations of the affected IL-17AA residues essentially coincides with the regions of both IL-17A and IL-17F previously shown to undergo significant structural changes on binding to IL-17RA. Substantially less conformational exchange was revealed by the NMR data for IL-17FF and IL-17AF. We propose that the markedly different conformational dynamic properties of the distinct functional IL-17 dimers plays a key role in determining their affinities for IL-17RA, with the more dynamic and plastic nature of IL-17AA contributing to the significantly tighter affinity observed for binding to IL-17RA. In contrast, the dynamic properties are expected to have little influence on the affinity of IL-17 dimers for IL-17RC, which has recently been shown to induce only small structural changes in IL-17FF upon binding.
- Published
- 2020
28. Brodalumab: an evidence-based review of its potential in the treatment of moderate-to-severe psoriasis.
- Author
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Coimbra, Susana, Figueiredo, Américo, and Santos-Silva, Alice
- Subjects
CELLULAR signal transduction ,MONOCLONAL antibodies ,PSORIASIS ,EVIDENCE-based medicine ,INVESTIGATIONAL drugs - Abstract
Advances in knowledge regarding the pathogenesis of psoriasis have allowed the development of a new class of agents known as biologic drugs. Data confirm that T helper (Th)17 and interleukin (IL)-17 signaling has a crucial role in the pathogenesis of the disease. High levels of IL-17 and Th17-related cytokines have been reported in psoriasis, leading to the suggestion of agents targeting IL-17 as a potential therapeutic strategy in psoriasis. Brodalumab is a human monoclonal antibody that targets IL-17 receptor A, blocking the effects of IL-17A, IL-17F, and IL-17E. Data from Phase I and Phase II clinical trials indicate that brodalumab has a favorable safety and tolerability profile, with strong clinical activity, suggesting that it is a potential tool for use in the treatment of moderate-to-severe psoriasis. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
29. Interleukin 17 receptor A haplotype analysis in chronic spontaneous urticaria: A preliminary study
- Author
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Rasha Abd El-Hamed Ibrahim, Eman A. Toraih, Omnia Emad Abdelsalam, Hesham A. Nada, Amal Fathy, Ranya Hassan, and Mona A Atwa
- Subjects
medicine.medical_specialty ,Dermatology ,Disease ,Interleukin-17 receptor ,Gastroenterology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Disease susceptibility ,0302 clinical medicine ,Quality of life ,Internal medicine ,medicine ,Humans ,Chronic Urticaria ,Allele ,Receptors, Interleukin-17 ,Angioedema ,business.industry ,Haplotype ,Haplotypes ,030220 oncology & carcinogenesis ,Chronic Disease ,Quality of Life ,Autologous serum skin test ,medicine.symptom ,business - Abstract
BACKGROUND Chronic spontaneous urticaria (CSU) is a distressing skin disease. Family clustering and heterogeneity in the onset and progression indicate that susceptibility to CSU is a complex trait. In this study, we performed haplotype analysis for one of the key player gene, IL17RA, for CSU to test the association with disease susceptibility and severity. METHODOLOGY The study included 70 CSU patients and 30 healthy controls. The severity of the disease was evaluated by autologous serum skin test (ASST) and urticaria activity score (UAS). ASST test was done and quality of life was assessed using a questionnaire. Allelic discrimination analysis for rs4819554 and rs879577 was performed using real-time polymerase chain reaction technology. RESULTS Carriers of rs4819554*G were more prone to develop CSU than its counterpart (P = .039), while rs4819554*A allele displayed more severe phenotype in the form of more prolonged disease duration (P = .040), concurrent angioedema (P
- Published
- 2020
30. Interleukin 17 Receptor a Haplotype Analysis in Chronic Spontaneous Urticaria
- Author
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Hesham A. Nada, Amal Fathy, Ranya Hassan, Rasha Abd El-Hamed Ibrahim, Omnia Emad Abdelsalam, Mona A Atwa, and Eman A. Toraih
- Subjects
business.industry ,Haplotype ,Immunology ,Medicine ,Interleukin-17 receptor ,business - Abstract
Background: Chronic spontaneous urticaria (CSU) is a distressing skin disease. Family clustering and heterogeneity in the onset and progression indicate that susceptibility to CSU is a complex trait. In this study, we performed haplotype analysis for one of the key player gene, IL17RA, for CSU to test the association with disease susceptibility and severity.MethodsThe study included 70 CSU patients and 30 healthy controls. The severity of the disease was evaluated by autologous serum skin test (ASST) and urticaria activity score (UAS). ASST test was done and quality of life was assessed using a questionnaire. Allelic discrimination analysis for rs4819554 and rs879577 was performed using Real-Time Polymerase Chain Reaction technology.Results: Carriers of rs4819554*G were more prone to develop CSU than its counterpart (p = 0.039), while rs4819554*A allele displayed more severe phenotype in the form of more prolonged disease duration (p = 0.040), concurrent angioedema (p < 0.001), higher level of treatment (p < 0.001), and higher score of quality of life (p < 0.001). Additionally, homozygote patients with rs879577*CC were associated with angioedema (p < 0.001). Haplotype analysis revealed that cohorts with both rs4819554*A and rs879577*T conferred protection against developing CSU (OR = 0.07, 95%CI = 0.01 - 0.32, p = 0.001).Conclusions: Our results showed that IL17RA gene polymorphisms might contribute to the increased susceptibility to CSU.
- Published
- 2020
31. Effects of Vibrio harveyi infection on serum biochemical parameters and expression profiles of interleukin-17 (IL-17) / interleukin-17 receptor (IL-17R) genes in spotted sea bass
- Author
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Haishen Wen, Yalong Sun, Yuan Tian, Yun Li, Arat Yanglang, Xuebin Mao, and Yang Liu
- Subjects
0301 basic medicine ,Fish Proteins ,Immunology ,Spleen ,Interleukin-17 receptor ,Biology ,Microbiology ,03 medical and health sciences ,Fish Diseases ,medicine ,Animals ,Sea bass ,Receptor ,Pathogen ,Vibrio ,Head Kidney ,Receptors, Interleukin-17 ,Vibrio harveyi ,Interleukin-17 ,04 agricultural and veterinary sciences ,biology.organism_classification ,Immunity, Innate ,030104 developmental biology ,medicine.anatomical_structure ,Organ Specificity ,Vibrio Infections ,040102 fisheries ,0401 agriculture, forestry, and fisheries ,Bass ,Interleukin 17 ,Transcriptome ,Developmental Biology ,Signal Transduction - Abstract
Vibrio harveyi is regarded as serious pathogen for marine fishes. To evaluate the physiological responses of spotted sea bass (Lateolabrax maculatus) after V. harveyi infection, four biochemical biomarkers including alanine amino transferase (ALT), albumin (ALB), total protein (TP) and glucose (GLU) were measured in serum. Our results showed that V. harveyi infection significantly influenced the concentration of ALT, ALB and GLU. Additionally, five interleukin-17 (IL-17) and five IL-17 receptors (IL-17R) genes were identified in spotted sea bass and their gene structures were characterized. Furthermore, the expression patterns of IL-17 and IL-17R genes were determined by qPCR in liver, intestine, spleen and head kidney after V. harveyi infection. All IL-17 and IL-17R genes exhibited time- and tissue-dependent expressions. Several tested genes were dramatically induced by V. harveyi treatment, particularly IL-17A/F1 in liver and head kidney, IL-17A/F2 in head kidney, IL-17RC in spleen with more than 10-fold increases, which suggested their potential essential roles against bacterial infection.
- Published
- 2020
32. Interleukin-17 Receptor A gene polymorphism does not increase the risk of Bacillus Calmette-Guérin osteitis
- Author
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Matti Korppi, Qiushui He, Alex-Mikael Barkoff, Kirsi Nuolivirta, Heini Huhtala, Johanna Teräsjärvi, and Eero Lauhkonen
- Subjects
Receptors, Interleukin-17 ,business.industry ,General Medicine ,Interleukin-17 receptor ,medicine.disease ,Polymorphism, Single Nucleotide ,Microbiology ,Adjuvants, Immunologic ,Pediatrics, Perinatology and Child Health ,Medicine ,Humans ,Gene polymorphism ,Osteitis ,business ,Gene - Published
- 2020
33. Aggravated Atherosclerosis and Vascular Inflammation With Reduced Kidney Function Depend on Interleukin-17 Receptor A and Are Normalized by Inhibition of Interleukin-17A
- Author
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Sibylle von Vietinghoff, Alexandra Helmke, Shuwang Ge, Rongjun Chen, Hermann Haller, Ari Waisman, Song Rong, and Johannes Nordlohne
- Subjects
0301 basic medicine ,medicine.medical_specialty ,lcsh:Diseases of the circulatory (Cardiovascular) system ,Il17ra, interleukin-17 receptor A (gene name) ,medicine.medical_treatment ,Interleukin-17 receptor ,macrophage ,030204 cardiovascular system & hematology ,Lesion ,PRECLINICAL RESEARCH ,03 medical and health sciences ,PCR, polymerase chain reaction ,0302 clinical medicine ,Internal medicine ,medicine ,Macrophage ,Receptor ,business.industry ,CKD, chronic kidney disease ,LDLr, low-density lipoprotein receptor ,IL, interleukin ,Blockade ,Endothelial stem cell ,030104 developmental biology ,Endocrinology ,Cytokine ,lcsh:RC666-701 ,Interleukin 17 ,medicine.symptom ,atherosclerosis ,Cardiology and Cardiovascular Medicine ,business ,interleukin 17 ,chronic kidney disease - Abstract
Visual Abstract, Highlights • Moderate renal impairment significantly increases atherosclerotic lesion size and leukocyte numbers, most markedly macrophages and T cells, in LDLr–/– mice. • IL-17 receptor A–deficient LDLr–/– mice are protected from the growth in lesion size and leukocyte infiltrate in renal impairment. • Monocytes, especially Ly6C/GR1HIGH cells, express high levels of IL-17 receptor A. • IL-17A increases monocyte adhesion to the aortic wall and enhances endothelial cell pro-inflammatory cytokine production. • Ablation of IL-17A or IL-17A blockade normalizes the inflammatory aortic wall infiltrate even in established atherosclerosis., Summary Effective therapy of atherosclerotic complications in patients with chronic kidney disease (CKD) is an unmet clinical need. Cardiovascular events are the most common cause of death. At a glomerular filtration rate ≤60 ml/min, these events are increased also after correction for common risk factors. Previous studies have reported enhanced vascular inflammation in mice and recently also in humans. Our current data show, in a mouse model of atherosclerosis in moderate renal impairment, that interleukin-17 receptor A is instrumental in this condition, and blockade of this pathway can normalize arterial inflammation even in advanced atherosclerosis.
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- 2018
34. Deficiency of interleukin-17 receptor A1 induces microbiota disruption in the intestine of Japanese medaka, Oryzias latipes
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Jun-ichi Hikima, Tomoya Kono, Masato Kinoshita, Masahiro Sakai, and Yo Okamura
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Physiology ,Japanese medaka (Oryzias latipes) ,Oryzias ,Intestinal immune system ,Interleukin-17 receptor ,Gut flora ,Interleukin 17 receptor A ,digestive system ,Biochemistry ,Microbiology ,Immune system ,RNA, Ribosomal, 16S ,Genetics ,medicine ,Animals ,Microbiome ,Receptor ,Molecular Biology ,Receptors, Interleukin-17 ,biology ,Microbiota ,Japanese Medaka ,16S rRNA-based metagenomic analysis ,biology.organism_classification ,medicine.disease ,Plesiomonas shigelloides ,Intestines ,Dysbiosis - Abstract
The mutual relationship between the intestinal immune system and the gut microbiota has received a great deal of attention. In mammals, interleukin-17A and F (IL-17A/F) are inflammatory cytokines and key regulators of the gut microbiota. However, in teleosts, the function of IL-17A/F in controlling the gut microbiota is poorly understood. We attempted to elucidate the importance of teleost IL-17 signaling in controlling gut microbiota. We previously established a knockout (KO) of IL-17 receptor A (RA) 1, a receptor for IL-17A/F, in the Japanese medaka (Oryzias latipes) using the CRISPR-Cas9 system and performed 16S rRNA-based metagenomic analyses using the anterior and posterior sections of the intestinal tract. The number of observed OTUs in the anterior intestine was significantly decreased in IL-17RA1 KO medaka compared to that in the wild-type (WT). Furthermore, β-diversity analysis (weighted UniFrac) revealed considerably different bacterial composition in the anterior intestine of IL-17RA1 KO compared to WT, with similar findings in α-diversity. Notably, the pathogen Plesiomonas shigelloides was significantly increased in the posterior intestine of IL-17RA1 KO medaka. These findings indicate that signaling via IL-17RA1 is required to maintain a healthy gut microbiota in teleosts and mammals. The involvement of IL-17RA1 in controlling the gut microbiota has been demonstrated, resulting in microbiome dysbiosis in IL-17RA1 KO medaka.
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- 2021
35. Genome-wide identification of interleukin-17 (IL-17) / interleukin-17 receptor (IL- 17R) in turbot (Scophthalmus maximus) and expression pattern analysis after Vibrio anguillarum infection
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Chao Li, Yiping Liu, Ting Xue, Xiaoyan Zhang, Ning Yang, Qiang Fu, and Min Cao
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Fish Proteins ,0301 basic medicine ,Vibrio anguillarum ,medicine.medical_treatment ,Immunology ,Interleukin-17 receptor ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Animals ,Amino Acid Sequence ,Receptor ,Gene ,Conserved Sequence ,Phylogeny ,Skin ,Vibrio ,Genetics ,Mucous Membrane ,Receptors, Interleukin-17 ,Innate immune system ,Gene Expression Profiling ,Interleukin-17 ,biology.organism_classification ,Up-Regulation ,Turbot ,030104 developmental biology ,Cytokine ,030220 oncology & carcinogenesis ,Flatfishes ,Signal Transduction ,Developmental Biology - Abstract
Interleukin-17 (IL-17) is a cytokine secreted by a variety of immune cells that plays an important role in host defense against pathogens. IL-17 usually activates downstream immune signaling pathway by binding to heterodimeric or homodimeric complex formed by IL-17 receptors (IL-17R). Describing the characteristics, tissue distribution of IL-17 and IL-17 receptor family members and their expression after pathogen infection will provide a reference for host defense against disease of turbot. In this study, six IL-17 family members and nine IL-17 receptor family members were identified by analyzing the turbot (Scophthalmus maximus) genome. Different from other vertebrates, most members of the IL-17 receptor family own two copies. Protein structure analysis showed that the six IL-17 family members contained typical "IL-17" domains, and the nine IL-17 receptor family members contained typical "SEFIR domain" or "IL17_R_N domain". Syntenic analysis revealed that all IL-17s and IL-17Rs were chromosomally conserved compared with other fish. The phylogenetic analysis further confirmed the evolutionary conservatism of different copies of IL-17C and IL-17Rs. Tissue distribution results showed that IL-17 and IL-17R genes were highly expressed in immune-related tissues. The expression of IL-17C and its receptor in the mucosal immune tissues after infection with V. anguillarum was analyzed subsequently. The results showed that they were significantly increased in the skin, the first tissue to resist V. anguillarum. The results are consistent with previous studies showing that IL-17 and IL-17 receptor play an important role in promoting innate immune response.
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- 2021
36. Inflammatory Mediators Alter Interleukin-17 Receptor, Interleukin-12 and -23 Expression in Human Osteoarthritic and Rheumatoid Arthritis Synovial Fibroblasts: Immunomodulation by Vasoactive Intestinal Peptide.
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Carrión, Mar, Pérez-García, Selene, Jimeno, Rebeca, Juarranz, Yasmina, González-Álvaro, Isidoro, Pablos, José Luis, Gutiérrez-Cañas, Irene, and Gomariz, Rosa P.
- Abstract
Aims: To assess the contribution of fibroblast-like synoviocytes (FLS) to the inflammatory joint microenvironment under different pathogenic stimuli and their potential to respond to interleukin (IL)-17 and to determine whether the neuroimmunomodulatory vasoactive intestinal peptide (VIP) is able to modulate IL-17 receptor (IL-17R) and related cytokines. Methods: The effect of proinflammatory cytokines [tumor necrosis factor α (TNFα) and IL-17] and Toll-like receptor (TLR) ligands [poly(I:C) and lipopolysaccharide (LPS)] on IL-17R expression and IL-12 and IL-23 production was studied in osteoarthritis (OA)- and rheumatoid arthritis (RA)-FLS, involved in Th1/Th17 differentiation. The effect of VIP was also determined. IL-17RA, IL-17RC, IL-12p35 and IL-23p19 expression was measured by real-time polymerase chain reaction. IL-12 and IL-23 protein levels were measured by ELISA in supernatant cultures. Results: TNFα, LPS and poly(I:C) induced an increase in IL-17RA in RA-FLS, whereas TNFα, TNFα plus IL-17 and poly(I:C) enhanced IL-17RC transcripts in FLS. VIP diminished the upregulated expression of IL-17RA in RA-FLS following TNFα and poly(I:C). TNFα, LPS and poly(I:C) increased IL-12 and IL-23 levels in cells derived from patients presenting both pathologies. However, IL-17A decreased IL-12 and augmented IL-23. VIP decreased IL-12p35 mRNA upregulation by poly(I:C) and IL-23p19 transcripts in LPS-treated FLS. Conclusions: Inflammatory cytokines and TLR ligands modulate IL-17R, IL-12 and IL-23 possibly favoring the cross talk between FLS and Th1/Th17 cells. The ability of VIP to counteract the enhancing effect of proinflammatory molecules on IL-17R and the IL-12 family of cytokines corroborates and amplifies the beneficial effect of this endogenous neuroimmunopeptide in rheumatic diseases. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
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- 2013
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37. Interleukin-17: A New Paradigm in Inflammation, Autoimmunity, and Therapy.
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Kramer, Jill M. and Gaffen, Sarah L.
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PERIODONTAL disease ,RHEUMATOID arthritis ,IMMUNE response ,INFLAMMATION ,AUTOIMMUNE diseases - Abstract
Chronic diseases, such as periodontal disease (PD) and rheumatoid arthritis (RA), are characterized by a robust immune response resulting in unresolved inflammation. Inflammation is mediated by proinflammatory cytokines; recently, a novel subset of T-helper (Th) cells was identified that plays a crucial role in inflammation and autoimmune disease. This population secretes several proinflammatory cytokines, including the novel cytokine interleukin (IL)-17, and, hence, has been termed "Th17-" Inflammatory cytokines are implicated in the progression of localized chronic infections, such as PD, and in serious systemic pathologies, such as diabetes, chronic obstructive pulmonary disease, and cardiovascular disease. IL-17 mediates inflammation through a receptor (IL-17R) composed of two subunits, IL-17RA and IL-17RC. Drugs that antagonize inflammatory cytokines are used therapeutically to down- regulate immune-mediated pathology in conditions such as RA, although not all patients respond well to this approach. Therefore, identification of potential novel therapeutic targets, such as the IL-17 signaling complex, may be clinically relevant for mitigating inflammatory pathology. However, the manner in which such a therapeutic may influence the onset and progression of PD is poorly understood. Therapeutics that antagonize inflammatory cytokines ameliorate inflammation and bone loss and may have broader implications for individuals with systemic diseases in which inflammation and autoimmunity predominate. J Periodontol 2007;78:1083-1093. [ABSTRACT FROM AUTHOR]
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- 2007
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38. Expression Profile of Immune-Associated Genes in Nasal Polyps.
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Xin Wang, Zhen Dong, Dong-Dong Zhu, and Bing Guan
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NASAL polyps , *NASAL tumors , *POLYPS , *GENE expression , *IMMUNE system , *INTERLEUKINS , *GENETICS - Abstract
Objectives: We performed this study to investigate the expression profile of immune-associated gems and to probe the role of related genes in the immune pathogenesis of nasal polyps. Methods: Microarray analysis was used to find the expression profile of 491 immune-associated genes in nasal polyps. In validation studies, immunohistochemical staining and Western blot analysis were used to detect interleukin (IL)-17 and IL-17 receptor (IL-17R) in nasal polyps and controls. Results: Eighty-seven genes were differentially expressed in the immune-associated gene profile of nasal polyps, and 15 genes showed differential expression in both chips. In nasal polyp tissues, IL-17 was expressed mainly in the cytoplasm of plasma cells and to a lesser degree in the prickle cell layer of the epithelium and the acinus of the serous gland. In turbinates, IL-17 was also expressed in the same location, but the expression of IL-17 in nasal polyps and that in turbinates differed significantly (p < 05). Both IL-17 and IL-17R displayed specific bands in nasal polyps and turbinates, but the bands of E-17 and L17R in nasal polyps were stronger than those in turbinates. Conclusions: The differentially expressed genes in immune-associated gene chips will provide clues about, and a theoretical foundation for, the pathogenesis of nasal polyps. Furthermore, IL-17 may play an important role in the occurrence of nasal polyps by overexpression. [ABSTRACT FROM AUTHOR]
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- 2006
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39. Altered expression of microRNAs in patients with pouchitis after restorative proctocolectomy
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Masaru Shinozaki, Masanori Nojima, Itaru Endo, Kiyoshi Yamaguchi, Hideaki Kimura, Keisuke Hata, and Emi Inoue
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Gene Expression ,Interleukin-17 receptor ,Pouchitis ,Inflammatory bowel disease ,Gastroenterology ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Intestinal mucosa ,Internal medicine ,microRNA ,Gene expression ,medicine ,Humans ,Intestinal Mucosa ,Receptors, Interleukin-17 ,business.industry ,Proctocolectomy ,Proctocolectomy, Restorative ,General Medicine ,Middle Aged ,medicine.disease ,Ulcerative colitis ,MicroRNAs ,030104 developmental biology ,Colitis, Ulcerative ,Female ,030211 gastroenterology & hepatology ,Surgery ,business - Abstract
Pouchitis is the most common long-term complication of restorative proctocolectomy with ileal pouch-anal anastomosis. We investigated alterations in the expression of microRNAs, noncoding RNAs that act as potent negative regulators of gene expression, in pouchitis. The subjects of this study were 16 patients with diagnosed pouchitis and 48 patients without pouchitis after restorative proctocolectomy, performed for ulcerative colitis. Total RNA was extracted from biopsies and microRNAs were quantified using a real-time polymerase chain reaction. The expression of microRNA 21 and 223 was higher, whereas that of microRNA 192 and 196a was lower, in the inflamed mucosa from the pouchitis patients than in the mucosa from the non-pouchitis patients. The levels of 14 microRNAs were significantly lower in the mucosa from the pouchitis patients, than in the non-inflamed proximal ileal mucosal samples. The expression of microRNA 192 was remarkably reduced in pouchitis. A significant negative correlation was found between microRNA 192 and interleukin 17 receptor A mRNA levels. Significant alteration in miRNA expression in line with inflammatory bowel disease was evident in the mucosa from the pouchitis patients. Interleukin 17 receptor A may be involved in the pathogenesis of pouchitis through the downregulation of microRNA 192.
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- 2017
40. The Effect of Interleukin-17 on the Proliferation and Invasion of JEG-3 Human Choriocarcinoma Cells.
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Pongcharoen, Sutatip, Niumsup, Pannika, Sanguansermsri, Donruedee, Supalap, Kwansuda, and Butkhamchot, Puntharee
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MICE , *CELLS , *PREGNANCY , *TROPHOBLAST , *CELL lines , *PROTEINS - Abstract
Problem As there has been a study in mice showing the expression of IL-17 by decidual cells and the status of IL-17 receptor expression in human pregnancy is not known, we hypothesized that IL-17 may regulate human trophoblast proliferation and invasion. Method of study JEG-3 cell line was used as a model for human trophoblast. Immunohistochemitry and reverse transcriptase polymerase chain reaction techniques were used to identify IL-17 receptor protein and mRNA, respectively. The effects of IL-17 on JEG-3 cell proliferation and invasion were tested using the BrdU incorporation and the Matrigel invasion assays, respectively. Results IL-17 increased the invasive capacity of JEG-3 cells but had no effect on the proliferation and multinucleated formation of JEG-3 cells. Conclusion In this JEG-3 cell model of human trophoblast, the IL-17R and IL-17 may have a regulatory role in trophoblast invasion. [ABSTRACT FROM AUTHOR]
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- 2006
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41. Successful treatment of severe psoriasis relapse with secukinumab (interleukin 17 A inhibitor) after abrupt brodalumab (interleukin 17 receptor inhibitor) discontinuation: A retrospective study evaluating long-term efficacy and safety
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Abdallah Khemis, Thierry Passeron, Henri Montaudié, Jean-Philippe Lacour, and Awatef Kelati
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Brodalumab ,02 engineering and technology ,Dermatology ,Interleukin-17 receptor ,Antibodies, Monoclonal, Humanized ,Severity of Illness Index ,Drug Administration Schedule ,Cohort Studies ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Internal medicine ,Psoriasis ,Humans ,Medicine ,Retrospective Studies ,Receptors, Interleukin-17 ,Dose-Response Relationship, Drug ,business.industry ,Antibodies, Monoclonal ,Retrospective cohort study ,021001 nanoscience & nanotechnology ,medicine.disease ,Long-Term Care ,Discontinuation ,Treatment Outcome ,Retreatment ,Monoclonal ,Female ,Secukinumab ,Patient Safety ,Interleukin 17 ,0210 nano-technology ,business - Published
- 2018
42. Molecular characterization and expression of two interleukin-17 receptor A genes on different chromosomes in Japanese medaka, Oryzias latipes
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Masahiro Sakai, Shuzo Sawada, Tomoya Kono, Jun-ichi Hikima, Natsuki Morimoto, and Yo Okamura
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0301 basic medicine ,Fish Proteins ,Receptors, Interleukin-17 ,biology ,Physiology ,Oryzias ,Edwardsiella tarda ,Interleukin-17 receptor ,Japanese Medaka ,biology.organism_classification ,Biochemistry ,Molecular biology ,Chromosomes ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Gene Expression Regulation ,Gene expression ,Animals ,Receptor ,Molecular Biology ,Gene ,030215 immunology ,Synteny - Abstract
In mammals, interleukin 17 (IL-17), which is produced mainly by Th17 cells, is a hallmark inflammatory cytokine that plays key roles in the protection against infection and intestinal mucosal immunity. The mammalian IL-17 receptor family comprises five members (IL-17RA–E). Of these, IL-17RA is important in the control of the bacterial microbiota in mucosal tissues, particularly in the intestine, where it acts as a receptor for IL-17A and -F. In this study, the nucleotide sequence of IL-17RA1 cDNA from Japanese medaka (Oryzias latipes) of the Cab strain was determined and compared to two IL-17RA cDNAs (i.e., IL-17RA1 and IL-17RA2) of Japanese medaka Hd-rR strain downloaded from NCBI. Hd-rR 17RA1 and IL-17RA2 were located on chromosome 23 and chromosome 6, respectively, and phylogenetic tree analysis revealed that teleost IL-17RA1 and IL-17RA2 were separated in different clusters. Synteny analysis revealed that Japanese medaka IL-17RA1 and mammalian IL-17RA are conserved. IL-17RA1 expression levels in the gills, intestine, whole kidney, skin, and spleen were significantly higher than those of IL-17RA2, suggesting that IL-17RA1 is an important functional receptor in mucosal immunity. Interestingly, the expression levels of both IL-17RA genes were notably higher in the posterior than in the anterior intestinal tract section. Furthermore, despite its lower basal expression, IL-17RA2 expression was significantly increased at 72 h post Edwardsiella tarda infection.
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- 2019
43. Interleukin 17 receptor E (IL-17RE) mediates Poly(inosinic-cytidylic) acid-induced inflammation in a mouse model of allergic lung inflammation
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Robert Bals, Giovanna Vella, Felix Ritzmann, Christoph Beisswenger, and Christian Herr
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Chemokine ,Lung ,biology ,business.industry ,medicine.medical_treatment ,Inflammation ,Interleukin-17 receptor ,CCL5 ,Cytokine ,medicine.anatomical_structure ,Immunology ,biology.protein ,Medicine ,Nasal administration ,Respiratory system ,medicine.symptom ,business - Abstract
Introduction: Interleukin 17 receptor E (IL-17RE) is specific to the epithelial cytokine interleukin-17C (IL-17C). Asthma exacerbation are frequently caused by viral infections. Polycytidylic acid (poly(I:C)) mimics viral infections through binding to TLR-3. We and others have shown that poly(I:C) induces the expression of IL-17C in respiratory epithelial cells. Aim: To investigate the function of IL-17RE in a mouse model of allergic lung inflammation. Methods: Wildetyp (WT) and IL-17RE deficient mice were sensitized and challenged with OVA to induce allergic lung inflammation. PolyI:C was applied intranasally. Levels of pulmonary cytokines and chemokines were analyzed 24 hours post polyI:C treatment. Results: There were no differences in the pulmonary concentrations of the cytokines CCL5, IL-5, and IL-13 and the chemokines MIP-2 and KC between WT and IL-17RE-/- mice in the absence of allergic lung inflammation 24 hours post polyI:C treatment. Treatment with polyI:C in the presence of allergic lung inflammation resulted in significantly increased concentrations of IL-15, IL-13, CCL5, MIP-2, and KC in WT mice compared with IL-17RE-/- mice. Summary: These results indicate that IL-17RE mediates virus-triggered lung inflammation in experiment asthma.
- Published
- 2019
44. Interleukin‐17/interleukin‐17 receptor axis elicits intestinal neutrophil migration, restrains gut dysbiosis and lipopolysaccharide translocation in high‐fat diet‐induced metabolic syndrome model
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Murilo S. Dias, Daniela Carlos, João Santana da Silva, Bernhard Ryffel, Paula Zaghetto de Almeida, Emanuelle Neiverth de Freitas, Jefferson A. Leite, Marcel R. de Zoete, Malena M. Perez, Camila A. Pereira, Larissa M. S. Martins, Simone G. Ramos, Enrico Cerioni Spiropulos Gonçalves, Rita C. Tostes, Universidade de Brasilia [Brasília] (UnB), Instituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento em Lisboa (INESC-ID), Instituto Superior Técnico, Universidade Técnica de Lisboa (IST)-Instituto de Engenharia de Sistemas e Computadores (INESC), Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Universidade de São Paulo (USP), UMR7355 Immunologie et Neurogénétique Expérimentales et Moléculaires, and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Lipopolysaccharides ,Male ,Chemokine ,medicine.medical_specialty ,Lipopolysaccharide ,Neutrophils ,[SDV]Life Sciences [q-bio] ,Immunology ,Adipose tissue ,Interleukin-17 receptor ,Gut flora ,Diet, High-Fat ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,INTESTINOS ,Intestinal mucosa ,Cell Movement ,Internal medicine ,medicine ,Immunology and Allergy ,Animals ,ComputingMilieux_MISCELLANEOUS ,2. Zero hunger ,Metabolic Syndrome ,Mice, Knockout ,Receptors, Interleukin-17 ,biology ,Chemistry ,Interleukin-17 ,Original Articles ,biology.organism_classification ,Intestines ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,biology.protein ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Dysbiosis ,Interleukin 17 ,Akkermansia muciniphila ,030215 immunology - Abstract
Sound evidence supports a role for interleukin‐17 (IL‐17) ‐producing γδ T cells and IL‐17‐producing helper T (Th17) cells in intestinal homeostasis, especially in intestinal barrier integrity. In the present study, we aimed to evaluate the role of IL‐17 cytokine in the regulation of intestinal immunity and obesity‐induced metabolic syndrome (MetS) in an experimental murine model. C57BL/6 wild‐type (WT) mice and mice lacking the IL‐17 cytokine receptor (IL‐17RA(−/−)) were fed either a control diet (CD) or a high‐fat diet (HFD) for 9 weeks. Our data demonstrate that IL‐17RA(−/−) mice are protected against obesity, but develop hyperglycemia, hyperinsulinemia and insulin resistance. In parallel, HFD‐fed IL‐17RA(−/−) mice display intense inflammation in the ileum compared with WT mice on the HFD. IL‐17RA(−/−) mice fed the HFD exhibit impaired neutrophil migration to the intestinal mucosa and reduced gene expression of the CXCL‐1 chemokine and CXCR‐2 receptor in the ileum. Interestingly, the populations of neutrophils (CD11b(+) Ly6G(+)) and anti‐inflammatory macrophages (CD11b(+) CX3CR1(+)) are increased in the mesenteric lymph nodes of these mice. IL‐17RA(−/−) mice on the HFD also display increased commensal bacterial translocation into the bloodstream and elevated lipopolysaccharide (LPS) levels in the visceral adipose tissue (VAT). Metagenomic analysis of bacterial 16S gene revealed increased Proteobacteria and Bacteroidetes phyla, the main representatives of Gram‐negative bacteria, and reduced Akkermansia muciniphila in the fecal samples of IL‐17RA(−/−) mice fed the HFD. Together, these data indicate that the IL‐17/IL‐17R axis drives intestinal neutrophil migration, limits gut dysbiosis and attenuates LPS translocation to VAT, resulting in protection to MetS.
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- 2018
45. A highly sensitive and selective impedimetric aptasensor for interleukin-17 receptor A
- Author
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Hyungjun Youn, Hunho Jo, Jian Jeong, Heehyun Lee, Kwanghyun Lee, Hae-Sim Park, Seong-Kyeong Kim, Seung-Hyun Kim, Changill Ban, and Jihyun Mok
- Subjects
0301 basic medicine ,Aptamer ,Biomedical Engineering ,Biophysics ,Metal Nanoparticles ,HL-60 Cells ,Nanotechnology ,Interleukin-17 receptor ,03 medical and health sciences ,Limit of Detection ,Wide dynamic range ,Electrochemistry ,Humans ,Electrochemical biosensor ,Electrodes ,Detection limit ,Receptors, Interleukin-17 ,Chromatography ,Chemistry ,Equipment Design ,General Medicine ,Aptamers, Nucleotide ,Electroplating ,Highly sensitive ,030104 developmental biology ,Colloidal gold ,Dielectric Spectroscopy ,Gold ,Biosensor ,Biotechnology - Abstract
Interleukin-17 receptor A (IL-17RA) has been recognized as a valuable biomarker for diverse diseases, including autoimmune diseases. In this work, an electrochemical biosensor with great sensitivity and selectivity toward IL-17RA was fabricated using an IL-17RA aptamer (Kd=14.00nM) for the first time. The aptasensor was manufactured using electrodeposition of gold nanoparticles, and then quantitative detection of IL-17RA was performed based on impedimetry. The developed sensor exhibited a superior analytical performance for IL-17RA with a wide dynamic range of 10-10,000pg/mL in buffer and a detection limit of 2.13pg/mL, which is lower than that of commercially available ELISA kits. In addition, we validated the high specificity of the designed aptasensor to only IL-17RA, which showed good sensitivity even in human serum solution. Furthermore, the detection of the differentiated HL-60 cells expressing IL-17RA was successfully performed. Clinical applicability of the sensor was also demonstrated utilizing neutrophils separated from asthma patients. It is expected that the fabricated aptasensor will become an excellent diagnostic platform for IL-17RA-mediated diseases.
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- 2016
46. EVALUATION OF THE POSSIBLE ROLE OF IL-17 AND ITS RECEPTOR IL-17R IN THE PATHOGENESIS OF ORAL LICHEN PLANUS
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Laila Rashid, Amira Maged Abdel Azim, Rasha Wagih Mosatafa, and Amal A. Hussine
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business.industry ,medicine.medical_treatment ,T cell ,Hematopoietic Tissue ,Interleukin-17 receptor ,medicine.disease ,Pathogenesis ,stomatognathic diseases ,Immune system ,Cytokine ,medicine.anatomical_structure ,stomatognathic system ,Immunology ,medicine ,General Earth and Planetary Sciences ,Oral lichen planus ,Interleukin 17 ,business ,General Environmental Science - Abstract
Introduction: Oral Lichen Planus (OLP) is considered a T cell mediated disease with unknown etiology. T helper cells appear to play an important role in the pathogenesis of OLP.Interleukin-17 (IL-17) is the signature cytokine of T helper (Th) cells. Recent studies suggested that IL-17 may be involved in the pathogenesis of OLPand homeostasis of tissues beyond the immune system.Interleukin-17 receptor (IL-17R) expression is working in disparate tissuessuch as articular cartilage, bone, meniscus, brain, hematopoietic tissue, kidney, lung, skin and intestine. Aim of the study: This study evaluated the possible correlation between serum and tissue levels of IL-17 as well as the expression of its tissue receptor in order to detect their possible role in the etio-pathogenesis of OLP. Subjects and methods: 20 patients with OLP and 10 healthy volunteers were recruited. Serum and tissue IL-17 levels were assessed by using an Enzyme Linked Immune-Sorbent Assay (ELISA), whileIL-17R gene expression was detected by quantitative real time polymerase chain reaction (qRT-PCR). Results : Results showed that the mean serum and tissue levels of IL-17 as well as mean tissue level of IL-17R in OLP were significantly higher compared to the controls (P value < 0.001),and there was a statistically significant positive (direct) correlation between serum IL-17 andboth tissue level of IL-17 and its tissue receptor. Discussion : This study demonstrated the increased expression of serum and tissue level of IL-17 and IL-17 tissue receptor in OLP patients, suggesting that IL-17 and its receptor in affected tissues may be associated with the pathogenesis of OLP and that IL-17 may be considered an important diagnostic pro-inflammatory cytokine in OLP. Conclusions and recommendations: Further studies are required to investigate the immune-pathologic mechanisms and therapeutic target of IL-17 in OLP.
- Published
- 2016
47. Conformational dynamics in interleukin 17A and 17F functional complexes is a key determinant of receptor A affinity and specificity.
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Waters, Lorna C., Veverka, Vaclav, Strong, Sarah L., Muskett, Frederick W., Dedi, Neesha, Lawson, Alastair D.G., Prosser, Christine E., Taylor, Richard J., Henry, Alistair J., and Carr, Mark D.
- Subjects
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CONFORMATIONAL analysis , *DIMERS , *BINDING sites , *CRYSTAL structure , *CELL communication , *INTERLEUKIN receptors , *PROTEIN conformation , *SPINE - Abstract
[Display omitted] • NMR studies of the IL-17 family are consistent with reported crystal structures. • Receptor binding sites in IL-17AA are characterised by conformational plasticity. • Strikingly less conformational dynamics is observed in IL-17AF and IL-17FF. • Structural plasticity governs the affinity of the IL-17 family for receptor A. • Conformational dynamics is unlikely to influence IL-17 affinity for receptor C. The proinflammatory cytokines IL-17A and IL-17F have been identified as key drivers of a range of human inflammatory diseases, such as psoriasis, which has led to several therapeutic antibodies targeted at IL-17A. The two cytokines have been shown to tightly associate as functional homo and hetero dimers, which induce signalling via the formation of a cell surface signalling complex with a single copy of both IL-17RA and IL-17RC. Striking differences in affinity have been observed for IL-17RA binding to IL-17AA, IL-17AF and IL-17FF, however, the functional significance and molecular basis for this has remained unclear. We have obtained comprehensive backbone NMR assignments for full length IL-17AA (79%), IL-17AF (93%) and IL-17FF (89%), which show that the dimers adopt almost identical backbone topologies in solution to those observed in reported crystal structures. Analysis of the line widths and intensities of assigned backbone amide NMR signals has revealed striking differences in the conformational plasticity and dynamics of IL-17AA compared to both IL-17AF and IL-17FF. Our NMR data indicate that a number of regions of IL-17AA are interconverting between at least two distinct conformations on a relatively slow timescale. Such conformational heterogeneity has previously been shown to play an important role in the formation of many high affinity protein-protein complexes. The locations of the affected IL-17AA residues essentially coincides with the regions of both IL-17A and IL-17F previously shown to undergo significant structural changes on binding to IL-17RA. Substantially less conformational exchange was revealed by the NMR data for IL-17FF and IL-17AF. We propose that the markedly different conformational dynamic properties of the distinct functional IL-17 dimers plays a key role in determining their affinities for IL-17RA, with the more dynamic and plastic nature of IL-17AA contributing to the significantly tighter affinity observed for binding to IL-17RA. In contrast, the dynamic properties are expected to have little influence on the affinity of IL-17 dimers for IL-17RC, which has recently been shown to induce only small structural changes in IL-17FF upon binding. [ABSTRACT FROM AUTHOR]
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- 2021
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48. Knockdown of Interleukin 17 Receptor A (IL‐17RA) in Paraventricular Nucleus of Hypothalamus Attenuates IL‐17‐induced Pressor Responses and Sympathetic Excitation
- Author
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Yiling Cao, Shun-Guang Wei, Yang Yu, and Robert B. Felder
- Subjects
medicine.medical_specialty ,Gene knockdown ,Endocrinology ,Paraventricular nucleus of hypothalamus ,Chemistry ,Internal medicine ,Genetics ,medicine ,Interleukin-17 receptor ,Interleukin 17 ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2020
49. Roles for Interleukin 17 and Adaptive Immunity in Pathogenesis of Colorectal Cancer
- Author
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Cynthia L. Sears, Fengyi Wan, Christopher Hurtado, and Franck Housseau
- Subjects
0301 basic medicine ,Colorectal cancer ,Inflammation ,Interleukin-17 receptor ,Adaptive Immunity ,medicine.disease_cause ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,medicine ,Animals ,Humans ,Intestinal Mucosa ,Hepatology ,business.industry ,Interleukin-17 ,Gastroenterology ,Th1 Cells ,Acquired immune system ,medicine.disease ,Gastrointestinal Microbiome ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Th17 Cells ,IL17A ,Interleukin 17 ,medicine.symptom ,business ,Carcinogenesis ,Colorectal Neoplasms - Abstract
Sporadic colorectal cancer is one of the most common and lethal cancers worldwide. The locations and functions of immune cells in the colorectal tumor microenvironment are complex and heterogeneous. T-helper (Th)1 cell–mediated responses against established colorectal tumors are associated with better outcomes of patients (time of relapse-free or overall survival), whereas Th17 cell–mediated responses and production of interleukin 17A (IL17A) have been associated with worse outcomes of patients. Tumors that develop in mouse models of colorectal cancer are rarely invasive and differ in many ways from human colorectal tumors. However, these mice have been used to study the mechanisms by which Th17 cells and IL17A promote colorectal tumor initiation and growth, which appear to involve their direct effects on colon epithelial cells. Specific members of the colonic microbiota may promote IL17A production and IL17A-producing cell functions in the colonic mucosa to promote carcinogenesis. Increasing our understanding of the interactions between the colonic microbiota and the mucosal immune response, the roles of Th17 cells and IL17 in these interactions, and how these processes are altered during colon carcinogenesis, could lead to new strategies for preventing or treating colorectal cancer.
- Published
- 2018
50. Is an anti‐interleukin‐17 receptor able to do the job when an anti‐interleukin‐12/23 has failed?
- Author
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H. Montaudié
- Subjects
Receptors, Interleukin-17 ,business.industry ,Antibodies, Monoclonal ,Dermatology ,Interleukin-17 receptor ,Antibodies, Monoclonal, Humanized ,Interleukin-12 ,Interleukin-23 ,Immunology ,Interleukin 12 ,Humans ,Psoriasis ,Medicine ,Ustekinumab ,business - Published
- 2019
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