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Forkhead box P3 (Foxp3) gene is an important means in the Treg cells function, in both maintenances of immune tolerance and regulation of response. Epigenetic modifications of the foxp3 gene at its regulatory regions control the chromatin accessibility for the transcription factors and other transcriptional regulators in order to control Foxp3 expression. In addition, the methylation status of CpG islands within the Foxp3 promoter and regulatory elements regulate the expression of Foxp3. This study was performed to assess the role of the foxp3 gene in patients with Behçet's syndrome (BS). Venous blood samples were collected from all participants and peripheral blood mononuclear cells (PBMC) were extracted through Ficoll-Hypaque method. Genomic DNA was randomly sheared by sonication and immunoprecipitated with a monoclonal antibody. The status methylation of the foxp3 gene was estimated in 108 blood samples of active BS patients and healthy individuals (controls); using methylation DNA immunoprecipitation (MeDIP) technique. Expression analysis was carried out; using Real-time PCR. The expression of foxp3 gene in the patients' group (mean±SD: 1.79±1.12) was significantly lower than the healthy group (mean±SD: 2.73±1.33) (p<001). Also, the methylation levels of Foxp3 promoter showed that its level in patients (mean±SD: 2.3±1.16) was higher than the healthy group (mean±SD: 1.85±0.59). However, this increase was not statistically significant (p>0.05). Also, these results indicated that increasing the amount of methylation of the foxp3 gene by reducing its expression leads to an increase and intensifying of the disease. The decrease in Foxp3 expression is possibly associated with hypermethylation of the gene, and it can be considered as a risk factor for BS. Future studies may be needed to identify the capability of specific DNA methylation alterations in this syndrome.

Leprosy, which is developed by the obligate intracellular Mycobacterium leprae (ML); has different manifestations, associated with the host immune responses. The protective immune response against ML includes T-cell-mediated immunity. The CTLA-4 has a great impact as a negative regulator of the immune response and maintenance of peripheral tolerance. This study analyzed the relationship between CTLA-4+49A/G gene polymorphism and clinical manifestation of leprosy disease and susceptibility among the Azeri population living Northwest Iran. One hundred and ninety-two leprosy patients and 185 healthy controls participated in the study. CTLA-4+49A/G genotyping was conducted via tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) analysis. The allelic and genotypic frequencies of +49A/G gene polymorphism were similar in controls and patients. However, older ages, older age of onset and over-representation in male were observed in lepromatous leprosy patient carriers of GG genotype. The current study demonstrates that although CTLA-4+49A/G polymorphism was not correlated with a higher genetic risk for leprosy, the presence of a GG genotype was associated with older ages, older age of onset and over-representation in male in Iranian Azeri population., (Copyright © 2017. Published by Elsevier B.V.)

Background: Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the Central Nervous System that is immunologically mediated in genetically susceptible individuals. IL-21, a cytokine produced by TCD4(+) cells, particularly by Th-17 cells, is believed to play an important role in the MS pathogenesis., Objective: This study was performed to investigate the impact of genetic polymorphisms in IL-21 gene on MS susceptibility and clinical profiles., Methods: Seventy Iranian patients with clinically definite relapsing-remitting MS and 110 age, sex and ethic matched controls were genotyped for IL-21 gene polymorphisms using PCR-RFLP method., Results: Our results showed that the IL-21 rs2221903 SNP is not polymorphic in our population. Also, the allelic and genotypic frequencies of the IL-21 rs2055979 did not differ significantly between the MS patients and controls (P = 0.413 and P = 0.565 respectively, and OR = 1.122, 95% CI = 0.79-1.87 for T allele). However, our results showed that IL-21 rs2055979 (G/T) T allele positive (TT+GT) MS patients had lower (PI ≤ 1.5) disease progression compared to rs2055979 T allele negative (GG) patients (P = 0.009)., Conclusion: Our results showed that no outstanding association exists between IL-21 alleles and susceptibility to MS. However, our clinical analysis showed significant association of IL-21 gene polymorphism with the progression of multiple sclerosis disease. Our results indicate that the G allele promotes, or the T allele protects against disease progression. To clarify the role of IL-21 rs2055979 in MS pathogenesis, further comprehensive studies with larger sample sizes among different ethnicity populations are recommended.

MS is an autoimmune disease and interleukin 13 (IL-13) has been proposed to be an important neuroprotective mediator in MS. Because of plausible effect of single nucleotide polymorphisms (SNPs) in expression level or biological activity of any cytokine, we sought to investigate association of IL-13 SNPs, C-1112T, A-1512C and G+2044A, with risk to MS. Sixty-eight RRMS patients and 110 healthy controls were involved in this study. After extraction of genomic DNA, frequency of genotypes and alleles were determined by PCR-RFLP and data were analyzed statistically. Results showed significant higher frequency of CC, CC, and AA genotypes and C, C, and A alleles of -1112CT, -1512AC and +2044GA SNPs respectively, in patients group. There was significant association between -1112C allele with onset age of MS. No significant association was seen between any of genotypes or alleles with expanded disability status scale (EDSS) of patients. Our findings showed significant association between three studied SNPs of IL-13 with susceptibility to MS in Iranian patients. More studies should be done on other IL-13 SNPs, and also polymorphisms of IL-13 receptor and other cytokines to determine the exact role of SNPs in protecting or predisposing of individuals for MS.

Background: Prostate cancer is the second leading malignancy worldwide and the second prominent cause of cancer-related deaths among men. Therefore, there is a serious necessity for finding advanced alternative therapeutic measures against this lethal malignancy. In this article, we report the cytotoxicity and the mechanism of cell death of the methanolic extract prepared from Echinophora platyloba DC plant against human prostate adenocarcinoma PC 3 cell line and Human Umbilical Vein Endothelial Cells HUVEC cell line., Methods: Cytotoxicity and viability of the methanolic extract were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and dye exclusion assay. Cell death enzyme-linked immunosorbent assay (ELISA) was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis and determine whether the mechanism involves induction of apoptosis or necrosis. The cell death was identified as apoptosis using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay and DNA fragmentation gel electrophoresis., Results: E. platyloba could decrease cell viability in malignant cells in a dose- and time-dependent manner. The IC50 values against PC 3 were determined as 236.136 ± 12.4, 143.400 ± 7.2, and 69.383 ± 1.29 μg/ml after 24, 36, and 48 h, respectively, but there was no significant activity in HUVEC normal cell (IC50 > 800 μg/ml). Morphological characterizations and DNA laddering assay showed that the methanolic extract treated cells displayed marked apoptotic characteristics such as nuclear fragmentation, appearance of apoptotic bodies, and DNA laddering fragment. Increase in an early apoptotic population was observed in a dose-dependent manner. PC 3 cell death elicited by the extract was found to be apoptotic in nature based a clear indication of TUNEL assay and gel electrophoresis DNA fragmentation, which is a hallmark of apoptosis., Conclusions: In summary, the E. platyloba extract attenuated the human prostate adenocarcinoma cell proliferation in vitro possibly by inducing apoptosis. E. platyloba is likely to be valuable for the treatment of human prostate adenocarcinoma.

Overexpression of Interleukin-17 (IL-17) family has been shown in a variety of autoimmune diseases. IL-25 (IL-17E), as a member of this family of cytokines, induces the overexpression of IL-13 and impedes Th17/IL-17 responses. In the present study potential single nucleotide polymorphisms (SNP) of IL-25, its serum level in Multiple Sclerosis (MS) patients have been surveyed. Blood samples were obtained from 100 Relapsing-Remitting MS cases, and 100 healthy controls. Serum levels of IL-25 were measured by ELISA. IL-25 exons 1 and 2 were sequenced. IL-25 serum levels investigation showed significant association in cases compared to controls. Molecular analysis of IL-25exons 1 and 2 depicted significant differences in polymorphisms of exon 2 between two groups of study. However, no significant differences were found in polymorphisms for IL-25 exon. These results demonstrate that serum levels of IL-25 are reduced in MS patients compared to controls. This is the first study in Iran that shows polymorphisms in IL-25 among MS patients. Considering the role of IL-25 in suppression of the effects of IL-17A and active phase of Experimental Autoimmune Encephalomyelitis (EAE) in vivo, this cytokine seems to have therapeutic potentials for autoimmune diseases like MS.

Objective: One-stage full-mouth disinfection technique (FMD) has been introduced to avoid cross-contamination between the treated and untreated regions between treatment sessions. Considering the role of inflammatory mediators in periodontitis, the aim of the present study was to compare the effects of FMD with the quadrant-wise scaling and root planing (Q-SRP) on serum levels of IL-17 and IL-1β in patients with moderate-to-severe chronic periodontitis., Materials and Methods: Twenty patients with chronic periodontitis were selected randomly and based on inclusion criteria in each group. In order to evaluate the periodontal status, the clinical parameters of bleeding on probing (BOP), clinical attachment level (CAL), probing depth (PD) and modified gingival index (MGI) were measured and recorded before treatment and at 2- and 4-month intervals after treatment. Immunologic parameters of the study such as IL-17 and IL-1β serum levels were determined by special laboratory kits at the same intervals. Data were analyzed by SPSS 15 statistical software. Statistical significance was defined at p<0.05., Results: The results showed a decrease in the means of IL-17 and IL-1β serum levels in both treatment modalities, with no statistically significant differences between the two study groups at the two time intervals (p>0.05). In the evaluation of periodontal parameters, all parameters exhibited clinical improvements in both groups, with no statistically significant differences between the two study groups (p>0.05)., Conclusion: Based on the results of the present study it was concluded that both FMD and Q-SRP techniques result in improvements in periodontal indexes and decreases in the serum levels of IL-17 and IL-1β inflammatory mediators.

Behçet Disease (BD) is an autoimmune disorder with recurrent ocular, vascular, central nervous system, articular, mucocutaneous, and gastrointestinal manifestations with unclear etiology and pathogenesis. The further characterization of inflammatory features of Behçet's disease may eventually lead to development of better treatment options. Clinical and laboratory observations suggested an important role of IL-17, IL-21 and neutrophil-mediated process in the pathogenesis of BD. New therapeutic modalities target specific and nonspecific suppression of the immune system. The various non-specific immunosuppressive drugs, used either alone or in combinations, frequently fail to control inflammation or maintain remissions. Due to encouraging clinical results (i.e. Antigenic specification, prolonged survival with acceptable levels of toxicity); antibody-based drugs could be effective for the clinical management of Behçet's disease.

Background: Multiple sclerosis (MS) is a CD4+ T cell-mediated autoimmune disease affecting the central nervous system (CNS). It was previously believed that Th1 cells were pathogenic T cells in experimental autoimmune encephalomyelitis (EAE). However, the functional role of Th1 cells in EAE has been reconsidered upon the discovery of IL-17-producing T cells which are considered as dominant effectors for inducing autoimmune tissue inflammation., Objective: The objective of this study was to assess the role of IL-17A and IL-17F in MS pathogenesis., Methods: We evaluated mRNA expression of IL-17A and IL-17F in thirty-five Iranian patients with relapsing-remitting MS (RRMS) and twenty-five healthy controls by Quantitative Real Time PCR., Results: The results of this study showed a twenty-fold increase in the expression of IL-17A mRNA in MS patients compared to the control group (p < 0.0001). IL-17F mRNA expression in MS patients was thirty three-times greater than the control group (p = 0.0008). IL-17A mRNA expression in the periphery was positively correlated with the expression of IL-17F transcripts in MS patients and controls (p < 0.01and p < 0.05, respectively)., Conclusion: These results indicate the critical role of Th17- mediated cytokines in the development of MS which was classically considered as a Th1-mediated disorder. The results of this study showed, for the first time, the importance of IL-17F in MS immunopathogenesis.