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In recent years the critical role of miRNAs has been established in many diseases, including autoimmune disorders. Immune thrombocytopenia purpura (ITP) is a predominant autoimmune disease, in which aberrant expression of miRNAs has been observed, suggesting that miRNAs are involved in its development. miRNAs could induce an imbalance in the T helper (Th)1/Th2 cell and Th17/Treg cell-related responses. Moreover, they could also cause alterations in Th9 and Th22 cell responses, and activate Tfh (T follicular helper) cell-dependent auto-reactive B cells, thus influencing megakaryogenesis. Herein, we summarize the role of immune-related miRNAs in ITP pathogenesis, and look forward to clinical applications.In recent years the critical role of miRNAs has been established in many diseases, including autoimmune disorders. Immune thrombocytopenia purpura (ITP) is a predominant autoimmune disease, in which aberrant expression of miRNAs has been observed, suggesting that miRNAs are involved in its development. miRNAs could induce an imbalance in the T helper (Th)1/Th2 cell and Th17/Treg cell-related responses. Moreover, they could also cause alterations in Th9 and Th22 cell responses, and activate Tfh (T follicular helper) cell-dependent auto-reactive B cells, thus influencing megakaryogenesis. Herein, we summarize the role of immune-related miRNAs in ITP pathogenesis, and look forward to clinical applications.

Objectives The potent anti-tumorigenic effects were attributed to ginger and there are some reports regarding the anti-cancer and immunomodulatory properties ginger-derived components. This study aimed to investigate the effects of zingerone on some immune-related parameters in an animal model of breast cancer. Methods The breast cancer was established in female BALB/c mice using a carcinogenic 4T1 cell line. At day 10 after cancer induction, tumor-bearing mice were divided into five groups and treated intraperitoneal (daily from days 11–30) with saline or zingerone (at doses 10, 20, 50 and 100 mg/kg/day). The mice were sacrificed on day 31 and the number of splenic Th1- and Treg cells, the expression of IFN-γ and TGF-β in the blood mononuclear cells, the antibody production against sheep red blood cell (SRBC) were determined using flow cytometry, real time-PCR and a standard hemagglutination assay, respectively. Results Zingerone at doses 50 and 100 mg/kg enhanced the number of splenic Th1 cells (p Conclusions Zingerone improve the T cell-mediated and antibody responses in a mouse model of breast cancer. The immunotherapeutic potentials of zingerone in cancers need more considerations.

BACKGROUND: During the Helicobacter pylori (HP) infection, the infiltration of the leukocytes into stomach mucosa is directed by locally produced chemokines that play a decisive role in infection outcome. The CagA is the most potent virulence factor of HP, so that the infection with CagA + strains is associated with more severe complications than infection with CagA - HP. OBJECTIVE: The aim was to determine the expression of chemokines CXCL10, CCL17, CCL20 and CCL22, and their receptors by CagA + HP- and CagA - HP-derived crude extract (HP-CE)-stimulated peripheral blood mononuclear cells (PBMCs) from peptic ulcer (PU) patients. METHODS: The serum and the PBMCs were collected from 20 HP-infected PU patients, 20 HP-infected asymptomatic subjects (HIA) and 20 non-infected healthy subjects (NHS). The PBMCs were cultured in absence of stimulator or with 10 µg CagA + HP crude extract (CagA + CE), 10 µg CagA - HP crude extract (CagA - CE). Chemokines and receptors were measured by ELISA and real time-PCR respectively. RESULTS: In PU patients, the production of chemokines CXCL10, CCL17, CCL20 and CCL22, and the expression of chemokine receptors CXCR3, CCR4 and CCR6 by CagA + CE-induced PBMCs were significantly higher than non-stimulated and CagA - CE stimulated cultures. The CXCL10 production by CagA + CE stimulated PBMCs from HIA subjects was significantly higher than the equal cultures from PU and NHS groups. The CCL17 and the CCL20 production by non-stimulated, CagA + CE stimulated, and CagA - CE stimulated PBMCs from PU subjects were significantly higher than the equal cultures from NHS and HIA groups. The CCL22 production by non-stimulated, CagA + CE stimulated and CagA - CE stimulated PBMCs from NHS group were significantly higher than the equal cultures from HIA and PU groups. The CagA + CE stimulated PBMCs from HIA subjects expressed lower amounts of CCR6 in comparison with CagA + CE stimulated PBMCs from NHS and PU groups. The serum levels CXCL10 and CCL20 in PU and HIA groups were significantly higher than NHS subjects. NHS and HIA groups displayed higher serum levels of CCL22 in comparison with PU patients. CONCLUSION: Results indicated that the CagA status of bacterium influence the expression of chemokines and receptors by HP-CE stimulated PBMCs from PU patients.

The ongoing conventional drugs for leishmaniasis treatment are insufficient. The present study aimed to assess 6-gingerol alone and in combination with amphotericin B on Leishmania major stages using experimental and in vivo murine models. Here, arrays of experimental approaches were designed to monitor and evaluate the 6-gingerol potential therapeutic outcomes. The binding affinity of 6-gingerol and IFN-γ was the basis for docking conformations. 6-Gingerol combined with amphotericin B represented a safe mixture, extremely leishmanicidal, a potent antioxidant, induced a remarkable apoptotic index, significantly increased the expression of the Th1-related cytokines (IL-12p40, IFN-γ, and TNF- α), iNOS, and transcription factors (STAT1, c-Fos, and Elk-1). In contrast, the expression of the Th2-related cytokines was significantly downregulated (p < 0.001). This combination was also potent when the lesion appearance was evaluated following three weeks of treatment. The histopathological and immunohistochemical patterns of the murine model represented clusters of CD4+ and CD8+ T lymphocytes which compressed and deteriorated the macrophages harboring Leishman bodies. The primary mode of action of 6-gingerol and amphotericin B involved broad mechanistic insights providing a coherent basis for further clinical study as a potential drug candidate for CL. In conclusion, 6-gingerol with amphotericin B synergistically exerted anti-leishmanial activity in vitro and in vivo and potentiated macrophages' leishmanicidal activity, modulated Th1- and Th2-related phenotypes improved the histopathological changes in the BALB/c mice infected with L. major. They elevated the leukocyte infiltration into the lesions. Therefore, this combination should be considered for treating volunteer patients with CL in clinical studies.

Background: The imbalanced expression of chemokines plays critical role in the development of Helicobacter pylori-mediated complications. Objectives: Our aim was to determine ginger extract (GE) effects on the expression of chemokines CCL17, CCL20, CCL22, and CXCL10, as well as CCR4, CCR6, and CXCR3 receptors by peripheral blood mononuclear cells (PBMCs) from H. pylori -infected patients with peptic ulcer (PU). Methods: Peripheral blood mononuclear cells were obtained from 20 patients with H. pylori-associated PU, 20 H. pylori-infected asymptomatic subjects (HAS), and 20 non-infected healthy subjects (NHS). The PBMCs were stimulated by 10 µg/mL of H. pylori-derived crude extract (HPCE) in the presence of 0, 10, 20, and 30 µg/mL of GE. After 36 hours, the supernatant and the RNA extracted from the cells were tested for chemokine concentration and chemokine receptor expression using ELISA and real-time PCR techniques, respectively. Results: In PU patients, treating HPCE-stimulated PBMCs with 10, 20, or 30 µg/mL GE reduced the production of CXCL10 (1.47, 1.5, and 1.53 folds, respectively, P < 0.001 for all), CCL20 (1.44, 1.62, and 1.65 folds, respectively, P < 0.003), and treatment with 30 µg/mL GE increased CCL17 (1.28-fold, P < 0.001) and CCL22 (1.59-fold, P < 0.001) production compared with untreated HPCE-stimulated PBMCs. In PU patients, the HPCE-stimulated PBMCs treated with 10, 20, or 30 µg/mL GE expressed lower levels of CXCR3 (1.9, 3, and 3.5 folds, respectively, P < 0.001) and CCR6 (2.3, 2.7, and 2.8 folds, respectively, P < 0.002) while treating with 10 µg/mL GE upregulated CCR4 (1.7 fold, P = 0.003) compared with untreated HPCE-stimulated PBMCs. Conclusions: Ginger extract modulated the expression of chemokines and their receptors in the PBMCs derived from H. pylori-infected PU patients. The therapeutic potentials of ginger for treating HP-related complications need to be further explored.

Background Detection of the mechanism of host/parasite interactions in unresponsive forms of anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica is helpful for immunotherapy and vaccine development. In the present study, the gene expression of toll-like receptors (TLRs), TNF-α, iNOS and also arginase (ARG) activity in monocytes from Glucantime unresponsive in comparison to responsive patients infected with L. tropica was investigated. Methods In this case–control study, patients with unresponsive (n = 10) and responsive (n = 10) ACL were recruited. Gene expression of TLR2, TLR4, TLR9, TNF-α and iNOS was analyzed in L. tropica-exposed monocytes. The level of ARG activity in both isolated promastigotes and the lysates of monocytes was also determined. Results L. tropica-exposed monocytes represented higher expression of all three TLRs and TNF-α and lower expression of iNOS compared to unexposed ones in both groups of patients. Results revealed a significant down-regulation of TLR2 and TNF-α and up-regulation of TLR9 expression in unresponsive isolates in comparison to responsive ones. Besides, ARG level showed a significant increase in L. tropica-stimulated monocytes and cultured promastigotes from unresponsive isolates versus responsive ones. Conclusions The decreased TLR2, TLR4, TNF-α and iNOS and the increased level of TLR9 expression in L. tropica-exposed monocytes from unresponsive isolates and also the increment in ARG activity in their promastigotes and monocytes, might possibly be involved in the severity of the disease and leading to Glucantime unresponsiveness.

The imbalance between pro and anti-inflammatory cytokines plays an important role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Thymus vulgaris (thyme) as a traditional medicinal plant has been reported to exert antimicrobial, antioxidant, and anti-inflammatory effects. Therefore, this study evaluated the modulatory effects of Thymus vulgaris on the clinical symptoms, histopathological scores, and the production of some anti-inflammatory (TGF-β, IL-4, and IL-10) and pro-inflammatory (IFN-γ, IL-6 and IL-17) cytokines in EAE model. EAE was induced by MOG35–55 peptide and mice were treated intra-peritoneally (i.p) with phosphate buffered saline (PBS) in the control group or thyme extract (50 or 100 mg/kg of body weight, every other day) in thyme-treated EAE groups, from day 0 to +21 of post MOG immunization. Mice were sacrificed at day 22, and splenocytes were isolated and re-stimulated in vitro with MOG in order to measure the cytokine production and proliferation of re-stimulated cells by enzyme linked immunosorbent assay (ELISA) method and WST-1 reagent, respectively. The clinical symptoms and histopathological scores of the CNS were lower in thyme-treated than EAE control group. Furthermore, the production of IFN-γ and IL-6 by splenocytes was lower in thyme-treated EAE than in the control group. The production of IL-10 and TGF-β increased in mice treated with thyme extract compared to the control group. In this study, we showed for the first time that the immunomodulatory effects of Thymus vulgaris in EAE model. Thus, the possible therapeutic potential of thyme for treatment of MS could be considered in future research.

Cutaneous leishmaniasis (CL) is a curable disease; however, due to various risk factors, unresponsiveness to CL treatments is inevitable. The treatment of CL has been firmly correlated with multiple determinants, such as demographical, clinical, and environmental factors, the host’s immune response, poor treatment adherence, the parasite’s genetic make-up, and Leishmania RNA virus. This study primarily focuses on the risk factors associated with different therapeutic outcomes following meglumine antimoniate (MA; Glucantime®) treatment and policy approaches to prevent unresponsiveness in CL patients with a focus on anthroponotic form (ACL). Findings suggest that effective preventive and therapeutic measures should be more vigorously implemented, particularly in endemic areas. Accordingly, extensive training is essential to monitor drug unresponsiveness regularly, especially in tropical regions where the disease is prevalent. Since humans are the fundamental reservoir host of ACL due to L. tropica, prompt detection, early diagnosis, and timely and effective treatment could help control this disease. Furthermore, major challenges and gaps remain: efficacious vaccine, new tools, and expert staff are crucial before CL can be definitively controlled.

Following inoculation of Leishmania, a protozoan parasite, into the skin of a mammal, the epidermal keratinocytes recognize the parasite and influence the local immune response that can give rise to different outcomes of leishmaniasis. The early keratinocyte-derived cytokines and keratinocytes-T cells interactions shape the anti-leishmanial immune responses that contribute to the resistance or susceptibility to leishmaniasis. The keratinocyte-derived cytokines can directly potentiate the leishmanicidal activity of monocytes and macrophages. As keratinocytes express MHC-II and enhance the expression of costimulatory molecules, these cells act as antigen-presenting cells (APCs) in cutaneous leishmaniasis (CL). Depending on the epidermal microenvironment, the keratinocytes induce various types of effector CD4+ T cells. Keratinocyte apoptosis and necrosis have been also implicated in ulceration in CL. Further, keratinocytes contribute to the healing of Leishmania-related cutaneous wounds. However, keratinocyte-derived IL-10 may play a key role in the development of post-kala-azar dermal leishmaniasis (PKDL). In this review, a comprehensive discussion regarding the multiple roles played by keratinocytes during leishmaniasis was provided, while highlighting novel insights concerning the immunological and pathological roles of these cells.

The COVID-19-, SARS- and MERS-related coronaviruses share many genomic and structural similarities. However, the SARS-CoV-2 is less pathogenic than SARS-CoV and MERS-CoV. Despite some differences in the cytokine patterns, it seems that the cytokine storm plays a crucial role in the pathogenesis of COVID-19-, SARS- and MERS. Monocytes and macrophages may be infected by SARS-CoV-2 through ACE2-dependent and ACE2-independent pathways. SARS-CoV-2 can effectively suppress the anti-viral IFN response in monocytes and macrophages. Since macrophages and dendritic cells (DCs) act as antigen presenting cells (APCs), the infection of these cells by SARS-CoV-2 impairs the adaptive immune responses against the virus. Upon infection, monocytes migrate to the tissues where they become infected resident macrophages, allowing viruses to spread through all organs and tissues. The SARS-CoV-2-infected monocytes and macrophages can produce large amounts of numerous types of pro-inflammatory cytokines and chemokines, which contribute to local tissue inflammation and a dangerous systemic inflammatory response called cytokine storm. Both local tissue inflammation and the cytokine storm play a fundamental role in the development of COVID-19-related complications, such as acute respiratory distress syndrome (ARDS), which is a main cause of death in COVID-19 patients. Here, we describe the monocytes and macrophage responses during severe coronavirus infections, while highlighting potential therapeutic interventions to attenuate macrophage-related inflammatory reactions in possible approaches for COVID-19 treatment., Graphical abstract Unlabelled Image, Highlights • A subset of monocytes and macrophages may be infected by SARS-CoV-2. • Coronavirus-infected monocyte can migrate to tissue and become infected macrophage. • Coronavirus-infected monocyte/macrophage produces high level of inflammatory factors. • Monocyte/macrophage-related cytokines promote organ inflammation and cytokine storm. • Local tissue inflammation and cytokine storm cause multi-organ failure in COVID-19.

IL-27 is a cytokine that exerts diverse effects on the cells of innate and adaptive immune systems. Chiefly expressed in macrophages and dendritic cells during the early phase of Leishmania infection, IL-27 contributes to the protection against L. major infection but suppresses the protective Th1 response against L. donovani, L. infantum, L. amazonensis and L. braziliensis infections, suggesting its functional duality. During the late stage of Leishmania infection, IL-27 limits the immunopathogenic reactions and tissue damages. Herein, we analyze the mechanism of the functional duality of IL-27 in the resistance or susceptibility to Leishmania infection, prompting IL-27 for anti-Leishmanial therapy.

Multiple sclerosis (MS) is characterized by chronic inflammatory response-induced demyelination of the neurons and degeneration of the axons within the central nervous system (CNS). A complex network of immunopathological-, inflammatory- and oxidative parameters involve in the development and advancement of MS. The anti-inflammatory, immunomodulatory and anti-oxidative characteristics of the ginger and several of its components have been indicated in some of experimental and clinical investigations. The possible therapeutic potentials of ginger and its ingredients in the treatment of MS may exert mainly through the regulation of the Th1-, Th2-, Th9-, Th17-, Th22- and Treg cell-related immune responses, down-regulation of the B cell-related immune responses, modulation of the macrophages-related responses, modulation of the production of pro- and anti-inflammatory cytokines, down-regulation of the arachidonic acid-derived mediators, interfering with the toll like receptor-related signaling pathways, suppression of the inflammasomes, down-regulation of the oxidative stress, reduction of the adhesion molecules expression, and down-regulation of the expression of the chemokines and chemokine receptors. This review aimed to provide a comprehensive knowledge regarding the immunomodulatory-, anti-inflammatory and anti-oxidative properties of ginger and its components, and highlight novel insights into the possible therapeutic potentials of this plant for treatment of MS. The review encourages more investigations to consider the therapeutic potentials of ginger and its effective components for managing of MS.

Introduction: Multiple Sclerosis (MS) is an inflammatory disorder caused by self-reactive Th1 lymphocytes, while Th2 cells may confer protection. The Th1 and Th2 cell differentiation are regulated by specific transcription factors, especially T-bet and GATA-3, respectively. This investigation aimed to measure the T-bet and GATA-3 expression by Peripheral Blood Mononuclear Cells (PBMCs) obtained from MS patients after specific and non-specific in vitro stimulation. Methods: The PBMCs were separated from 22 patients with MS and 20 healthy individuals. They were cultured at 37°C for 24 h in the absence of a stimulator or in the presence of Myelin oligodendrocyte Glycoprotein (MOG) or Phytohemagglutinin (PHA) at a concentration of 10 μg/mL. Then the T-bet and GATA-3 expression was measured by real time-PCR. Results: The T-bet expression was enhanced, while the GATA-3 expression diminished. Therefore the expression of T-bet/GATA-3 ratio diminished in not-stimulated, MOG-stimulated and PHA-stimulated PBMCs from MS patients compared with equal cultures from the healthy individuals (P

Helicobacter pylori (H. pylori) is one of the most prevalent human pathogen and a persistent infection with this bacterium causes common pathologies, such as gastritis or peptic ulcers, and also less common but more serious pathologies, such as gastric cancer or gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The clinical outcome of gastrointestinal infection sustained by H. pylori is determined by the reciprocal interactions between virulence factors of the bacterium and host factors, including immune response genes. Although H. pylori induces a strong immune response, the bacterium is not eliminated. The eradication failure could be attributed to the bacterial capability to regulate helper T (Th) cell-related responses. H. pylori specific CD4+ T cells play a fundamental role in regulating host immunity and immunopathologic events. It has been documented that Th1, Th2, Th9, Th17, Th22 and T regulatory (Treg) cells, separately or in coordination with each other, can affect the outcome of the infection sustained by of H. pylori. Some studies indicated that both Th1 and Th17 cells may be protective or pathogenic, whereas Treg and Th2 cells perform anti-inflammatory impacts during H. pylori infection. This review gathers recent information regarding the association of the CD4+ T cells–mediated immunological responses and the clinical consequence of H. pylori infection.

Objectives: A spectrum of immunomodulatory properties was attributed to vitamin D (VD). Here, the VD effects on expression of some Th17 cell- related cytokines, chemokines and chemokine receptors were investigated in experimental autoimmune encephalomyelitis (EAE). Methods: One group of C57BL/6 mice, considered as healthy group, was treated with phosphate buffered saline (PBS). EAE was induced in other three groups and treated from day +3 to +30 with PBS, olive oil (VD vehicle) or 200 ng of VD. At day 31, the expression of interleukin-17 (IL-17), IL-23, chemokine (C-C motif) ligand 20 (CCL20), CCL22, CC chemokine receptor 4 (CCR4) and CCR6 in spinal cord and serum IL-17 and IL-23 levels were measured by real-time PCR and ELISA, respectively. Results: The expression of IL-17, IL-23 P19, IL-23 P40, CCL20, CCL22 and CCR4 in spinal cord and serum IL-17 and IL-23 levels in PBS-administrated EAE mice were significantly increased compared with healthy group. In EAE mice treated with VD, the expression of aforementioned parameters was significantly reduced in comparison with PBS-administrated EAE mice. Conclusion: VD down-regulates the expression of some inflammatory cytokines, chemokines and chemokine receptors in EAE mice. The possible therapeutic potential of VD in multiple sclerosis can be considered in future investigation.

Infection with the same species of Leishmania (L)donovani causes different manifestations including visceral leishmaniasis (VL) and post kala-azar dermal leishmaniasis (PKDL), indicating that the host-related immunological parameters perform a decisive role in the pathogenesis of diseases. As PKDL is a reservoir of the parasite, a better understanding of the host immune responses is necessary to restrict the L. donovani transmission. The proper local production of Th1 cell-related cytokines (including IFN-γ, TNF-α and IL-12), Th17 cell-derived cytokines (such as IL-17A, IL-17F and IL-22), and CD8+ cytotoxic T lymphocyte (CTL)-derived IFN-γ are protective against PKDL. However, dominant production of regulatory CD4+ T cell-derived cytokines (such as IL-10 and TGF-β), Th2 cell-derived cytokines (such as IL-4/IL-13), M2 macrophage-derived cytokines (such as IL-4 and IL-10), keratinocyte-derived IL-10, regulatory CD8+ T cell-derived IL-10, and dendritic cell-derived IL-10, IL-27 and IL-21 can contribute to the parasite persistence and PKDL development. Understanding of the T cell-related cytokine network within PKDL lesions gives rise to novel insights concerning the role of each cytokine in the protection or susceptibility to disease. Manipulation of the cytokine network can be considered as an interesting immunotherapeutic strategy for the treatment of L. donovani-mediated PKDL.

The potential exists to improve treatment through characterization of tumor stem cells and identification of therapeutic targets Using OCT-4 and NANOG genes. Here we have synthesized and investigated the potential of; New Indole-3-carbaldehyde derivative (NI-3-CD) in inhibiting the expression of self-renewal regulatory factors and cancer stem cell gene in a leukemia cell line NB4.The NB4 cells were cultured in RPMI1640 medium contained NI-3-CD and I3F (15.12-1000μg/mL) for 24, 48 and 72h. Inhibition of cell proliferation was assessed by trypan blue staining technique and MTT assay. The percentage of apoptotic cells was determined by flow cytometry analysis using Annexin V/PI apoptosis detection kit. The fold changes of NANOG/OCT4 expression against β-actin were determined by real-time-PCR technique. Western blotting analysis was also applied for evaluating the expression of NANOG/OCT4 at protein level. Data were analyzed by student t and repeated measure tests. Differences were considered significant if (P0.01).There was a significant difference in cell viability, when various concentrations of NI-3- were used for 24, 48 and 72h in comparison to I3C regarding the cellular viability. Furthermore, the NI-3-CD, had markedly elevated anticancer activity than I3C (IC50 values for novel I3C in 24, 48 and 72h were 225.77, 123.13 and 63.72M respectively while for I3C were 728.05, 407.82 and 277.92M respectively). Flow cytometry results exhibited an obviously significant augmentation in apoptotic NB4 cells. Real Time- PCR analysis indicated that the expression of NANOG/OCT4 was down regulated in compare to untreated control cells and I3C treated cells (P0.05). In concert with RT-PCR, western blot analysis showed that the OCT4 expression in NI-3-CD treated cells was also significantly decreased in compare to both untreated control cells and I3C treated cellular populations.Our results imply that NI-3-CD treatment decreases the sphere-forming ability of NB4 cells. In summary, this study provides valuable information on the presence of stem-cell genes expression in NB4 cells.

Background Atopic dermatitis (AD) is an inflammatory skin disease which may be due to the imbalance between Th1-, Th2 and Treg cell-related immune responses. Evidences suggest that appropriate stimulation with probiotics may correct the skewed immune response in children with AD. The aim was to determine the effects of the yogurt culture lactobacillus Bulgaricus on the secretion of Th1/Th2/Treg type cytokines by PBMCs from children with AD. Methods L. Bulgaricus was cultivated on MRS broth. The PBMCs from 20 children with AD were separated by Ficoll-Hypaque centrifugation and co-cultured with different concentrations of UV killed bacteria in RPMI-1640 plus 10% FCS for 48/72 h. The levels of IL-10, IL-4, IL-12 and IFN-γ were measured in supernatant of PBMCs by ELISA. Results L. Bulgaricus significantly up-regulated the secretion of IL-10, IL-12 and IFN-γ, whereas decreased the secretion of IL-4 by PBMCs at both incubation times 48 h/72 h and both bacteria:PBMCs ratios 100:1/50:1, compared to control (p Conclusion These data show that L. Bulgaricus may modulate the secretion of Th1-, Th2-Treg-related cytokines in AD patients. Therefore, the possible potential therapeutic of L. Bulgaricus for treatment of AD should be consider in further investigation.

Background Aging is usually associated with increased levels of oxidants, and may result in damages caused by oxidative stress. There is a direct relationship between aging and increased incidence of inflammatory diseases. The present research intended to study the anti-aging and anti-inflammatory effects of the drug G2013 (guluronic acid) at low and high doses on the genes expression of a number of enzymes involved in oxidative stress (including SOD2, GPX1, CAT, GST, iNOS, and MPO) in peripheral blood mononuclear cells (PBMCs) of healthy individuals under in vitro conditions. Methods Venous blood samples were taken from 20 healthy individuals, the PBMCs were isolated and their RNAs extracted and their cDNAs were synthesized, and the genes expression levels were measured using the qRT-PCR technique. Results Our results indicated that this drug could, at both low and high doses, significantly reduce the expression of the genes for SOD2, GPX1, CAT, and GST compared to the LPS group ( p 0.0001). Moreover, it was noticed that the drug is able to significantly reduce gene expression levels at the high dose and at both doses (low and high), for iNOS and MPO compared to the LPS group ( p Conclusions The present research showed that G2013, as a novel NSAID drug with immunomodulatory properties, could modulate the expression levels of the genes for SOD2, GPX1, CAT, GST, iNOS, and MPO, to the level of healthy gene expression, and possibly it might reduce the pathological process of aging and age-related inflammatory diseases.

Vitamin D has potent immunoregulatory effects due to the expression of its receptor on the majority of immune cells. The aim was to evaluate the association of the vitamin D status with the persistence of anti-HBs antibody and immune response to booster immunization at 20years after primary vaccination with hepatitis B (HB) vaccine.Blood samples were collected from 300 adults 20years after completion of the primary HB vaccination in infancy. The serum levels of vitamin D and anti-HBs antibody were measured by ELISA. A single booster dose of a recombinant HB vaccine was administered to a total of 138 subjects, whose anti-HBs titer was10IU/L. The sera of revaccinated subjects were re-tested for anti-HBs antibody, 4weeks after booster vaccination.At 20years after primary vaccination, the mean vitamin D concentrations were significantly higher in seroprotective subjects as compared to non-seroprotective individuals (P0.01). The levels of anti-HBs were significantly increased with advanced concentrations of vitamin D (P0.01). Overall, 125/138 (90.6%) of the revaccinated subjects showed an anamnestic response to booster vaccination. The concentrations of vitamin D were significantly higher in subjects with an anamnestic response to booster vaccination as compared with subjects without this response (P0.01).Vitamin D status may influence the persistence of anti-HBs antibody and durability of protection after primary vaccination with a recombinant HB vaccine in infancy.

Toll-like receptors (TLRs) are a subset of pattern recognition receptors (PRR) in innate immunity and act as a connecting link between innate and adaptive immune systems. During Leishmania infection, the activation of TLRs influences the pathogen-specific immune responses, which may play a decisive role in determining the outcome of infection, toward elimination or survival of the pathogen. Antigen-presenting cells (APCs) of the innate immune system such as macrophages, dendritic cells (DCs), neutrophils, natural killer (NK) cells, and NKT cells express TLR2, which plays a crucial role in the parasite recognition and elicitation of immune responses in Leishmania infection. Depending on the infecting Leishmania species, the TLR2 pathways may result in a host-protective or a disease-exacerbating response. While Leishmania major and Leishmania donovani infections trigger TLR2-related host-protective and non-protective immune responses, Leishmania mexicana and Leishmania infantum infections are reported to elicit TLR2-mediated host-protective responses and Leishmania amazonensis and Leishmania braziliensis infections are reported to evoke a disease-exacerbating response. These findings illustrate that TLR2-related effector functions are diverse and may be exerted in a species- or strain-dependent manner. TLR2 agonists or antagonists may have therapeutic potentials to trigger the desired immune response during leishmaniasis. In this review, we discuss the TLR2-related immune responses during leishmaniasis and highlight the novel insights into the possible role of TLR2-driven resistance or susceptibility to Leishmania.

The extended infection with Helicobacter pylori (H. pylori), one of the most frequent infectious agents in humans, may cause gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. During H. pylori infection, different kinds of inflammatory cells such as dendritic cells, macrophages, neutrophils, mast cells, eosinophils, T cells and B cells are accumulated into the stomach. The interactions between chemokines and their respective receptors recruit particular types of the leukocytes that ultimately determine the nature of immune response and therefore, have a main influence on the consequence of infection. The suitable production of chemokines especially in the early stages of H. pylori infection shapes appropriate immune responses that contribute to the H. pylori elimination. The unbalanced expression of the chemokines can contribute in the induction of inappropriate responses that result in the tissue damage or malignancy. Thus, chemokines and their receptors may be promising potential targets for designing the therapeutic strategies against various types H. pylori-related gastrointestinal disorders. In this review, a comprehensive explanation regarding the roles played by chemokines in H. pylori-mediated peptic ulcer, gastritis and gastric malignancies was provided while presenting the potential utilization of these chemoattractants as therapeutic elements.

Hyper-inflammatory responses, lymphopenia, unbalanced immune responses, cytokine storm, large viral replication and massive cell death play fundamental roles in the pathogenesis of COVID-19. Extreme production of many kinds of pro-inflammatory cytokines and chemokines occur in severe COVID-19 that called cytokine storm. Signal transducer and activator of transcription-3 (STAT-3) present in the cytoplasm in an inactive form and can be stimulated by a vast range of cytokines, chemokines and growth factors. Thus, STAT-3 can participate in the induction of inflammatory responses during coronavirus infections. STAT-3 can also suppress anti-virus interferon response and induce unbalanced anti-virus adaptive immune response, through influencing Th17-, Th1-, Treg-, and B cell-mediated functions. Furthermore, STAT-3 can contribute to the M2 macrophage polarization, lung fibrosis and thrombosis. Moreover, STAT-3 may be directly targeted by some virus-derived protein and operate as a pro-viral or anti-viral element in a virus-specific process. Here, the possible contribution of STAT-3 to the pathogenesis of COVID-19 was explained, while providing potential approaches to target this transcription factor in an attempt for COVID-19 treatment.

The Th1- and Treg cell-related immune responses play key roles in the modulation of Th2 cell-related allergic disorders. The aim was to evaluate the effects of CPG, MPLA, and BCG on the number of Th1-, Th2-, and Treg cell-related parameters in an animal model of asthma. BALB/c mice were divided into five groups and immunized subcutaneously (SC) on days 1, 15, and 22 with allergen Derp2. Three groups of mice were pretreated SC on days 0, 14, and 21 with CPG, CPG + MPLA, or CPG + BCG. All mice were then challenged intranasally with Derp2 on days 28-37. Blood samples were collected from the retro-orbital sinus, on days 0, 23, and 40. The serum levels of IL-4, IFN-γ, IgE, and IgG2a were measured using ELISA technique. The blood number of Th1 and Treg cells was determined using flow cytometry. At the sensitization phase, the number of Th1 and the serum levels of IFN-γ and IgG2a were significantly increased in the Derp2-sensitized group pretreated with CPG plus MPLA, and the number of Treg cells was significantly elevated in Derp2-sensitized mice pretreated with CPG or CPG plus MPLA as compared with that in Derp2-sensitized control mice. At the challenge phase, the number of Th1 was significantly elevated in Derp2-sensitized mice pretreated with CPG plus MPLA, CPG plus BCG, or CPG; the count of Treg cells was significantly increased in Derp2-sensitized mice pretreated with CPG plus BCG group; and the levels of IFN-γ and IgG2a were significantly enhanced in the Derp2-sensitized group pretreated with CPG plus MPLA in comparison with those in Derp2-sensitized control mice. The scores of inflammation and mucus secretion in the lung were significantly decreased in the Derp2-sensitized group pretreated with CPG, BCG, and CPG plus MPLA in comparison with those in the Derp2-sensitized control group. These results showed that BCG, MPLA, and CPG modulate Th1-, Th2-, and Treg-related parameters and ameliorate lung inflammatory parameters in a mouse model of asthma.

There are some evidences for the immunomodulation disorders in the response to intestinal microbiota in inflammatory bowel disease. Yogurt is a fermented milk product made with a starter culture consisting of different probiotics which could be colonized in intestine. However, the role of probiotics in the aetiopathogenesis of ulcerative colitis (UC) has not been clarified. To determine how the immune system responds to these bacteria this study was planned.Bifidobacterium lactis BB-12 (B. lactis) and Lactobacillus acidophilus LA-5 (L. acidophilus) were cultivated on MRS broth. PBMCs of 36 UC patients were separated by Ficoll-Hypaque centrifugation and co-cultured with different concentrations of UV killed bacteria in RPMI-1 640 plus 10% FCS for 48/72 h. IL-10, TGF-β, IFN-γ and TNF-α were measured in supernatant of PBMCs by ELISA.Both bacteria significantly augmented IL-10, TGF-β, IFN-γ and TNF-α compared to control (p0.001). The secretion levels of IL-10 and TGF-β by B. lactis- compared to L. acidophilus-stimulated PBMCs were significantly higher (p0.05, p0.01 respectively). The secretion levels of TNF-α and IFN-γ by PBMCs after 72 h were significantly lower compared to 48 h stimulation by B. lactis (p0.001, p0.035 respectively).These data show that both probiotics may trigger the pro- and anti-inflammatory immune response of UC patients. It seems that IL-10/TGF-β uprising by B. lactis could be the reason of TNF-α/IFN-γ reduction. Therefore albeit B. lactis still stimulates the effector Th cells but because of more stimulatory effect on Tregs, it could be a good potential therapeutic candidate for further investigation.

Tumor cells escape from immune recognition by several mechanisms such as down-regulating of MHC class I molecules, losing of tumor antigens, etc. The purpose of cancer immunotherapy is to robust or reconstruct the capacity of the immune system to recognize and kill tumor cells by overwhelming the mechanisms by which tumors escape the immune response. One of the novel immunotherapeutic strategies were used to potentiate NK- and T cell functions is chimeric antigen receptor (CAR). CARs are composed of an antigen-binding domain of a molecule such as an antibody (that binds to a tumor associated antigens expressed on the surface of tumor cells) and an intracellular T cell activation domain. The CARs provide the recognition of target antigen in a MHC-independent manner. CAR-armed T cells may be unable to kill their targets in the absence of co-stimulators like NK cells. On the other hand, CAR-armed NK cells may also be unable to destroy their targets without receiving help signals from Th cells. Thus, if CAR-armed NK cells use together with CAR-armed T cells, NK cells will be aggregated to the tumor site. Thus, not only CAR T cells will obtain the necessary cytokines/costimulators from NK cells, but also other tumor specific T cells will be primed by recognition of tumor specific antigen (TSA) associated with MHC class I. These new specific primed T cells probably combat against tumor cells which have lost their TAAs that CAR-T cells are redirected to them.

The immunopathologic responses play a major role in the development of H. pylori (HP)-related gastrointestinal diseases. IL-37 is an anti-inflammatory cytokine with potent suppressive effects on innate and adaptive immune responses. Here, we investigated the IL-37 levels and two single nucleotide polymorphisms (SNPs) including rs3811047 and rs2723176 in IL-37 gene in HP-infected peptic ulcer (PU) patients to identify any relationship. Three groups, including 100 HP-infected PU patients, 100 HP-infected asymptomatic (AS) subjects and 100 non-infected healthy control (NHC) subjects were enrolled to study. Serum IL-37 levels and the genotyping at rs3811047 and rs2723176 were determined using ELISA and SSP-PCR methods, respectively. Significantly higher IL-37 levels were observed in PU patients compared with AS and NHC groups (P 0.0001). In both PU and AS groups, the CagA

Background: One of the most important limiting factors affecting the efficacy of treatment using monoclonal antibodies (mAbs) is their immunogenicity to the patients that may influence the diagnostic and therapeutic process. Objectives: This study determined the unwanted immunologic response to the presence of antibody against some theraputic agents made following taking mAbs in patients with malignancy. Methods: Blood samples were collected from patients with cancer, including 32 patients with lymphoma or leukemia, 43 patients with breast cancer, and 23 patients with adenocarcinoma (colon or ovarian cancer) while receiving treatment with Rituximab, Trastuzumab, and Bevacizumab, respectively. Serum levels of human antibodies against the mentioned mAbs were determined by the standard sandwich ELISA method designed in the research. Results: The presence of human antibodies against the mentioned mAbs was detected in 4 out of 32 (12.5%) Rituximab-treated patients and 7 out of 43 (16.3%) Trastuzumab-treated patients with a mean ± SD titer of 2.33 ± 0.37 AU/mL and 1.2 ± 0.21 AU/mL, respectively. The probability for the presence of anti-mAb in patients treated with Rituximab alone was significantly higher than patients, who took concomitantly Rituximab and once or more chemotherapeutic agents (26.6% vs. 0.0%; P < 0.02). None of Bevacizumab-treated patients, as was anticipated, developed antibody against the administrated mAb. Conclusions: The results of this study indicates the production of antibody against therapeutic mAbs Rituximab and Trastuzumab in a number of treated patients and this may influence their efficacy of treatment. The production of the human anti-mAb may be suppressed by chemotherapeutic drugs in Rituximab-treated patients and this phenomenon may be considered as a bonus effect during treatment. Bevacizumab did not show immunogenicity in the treated patients.

Toll-like receptors (TLRs) play principle roles in recognition of autologous components which have been pointed as the danger-associated molecular patterns (DAMP) and microbial components which are identified as pathogen associated molecular patterns (PAMP).The infiltration of various inflammatory cells such as dendritic cells, lymphocytes (CD4+ T, CD8+ T as well as B cells), monocytes and macrophages occur into the central nervous sys­tem (CNS) during multiple sclerosis (MS) and its animal model named experimental autoimmune encephalomyelitis (EAE). The infiltrated leukocytes and residential cells of the CNS express several TLRs (especially TLR2) and their expression are elevated in MS and EAE. TLR2 recognizes a large variety DAMP and PAMP molecules due to its ability to create heterodimers with TLR1, TLR6 and probably TLR10. A wide spectrum of DAMP molecules, including heat shock protein 60 (HSP60), HSP70, high mobility group box 1 (HMGB1), β-defensin 3, surfactant protein A and D, eosinophil-derived neurotoxin, gangliosides, serum amyloid A, hyaluronic acid and biglycan are identified by TLR2, whose their expression is increased in MS patients. TLR2 may contribute in the development of MS and EAE diseases through the reinforcement of Th1/Th17 cell-related responses, downregulation of regulatory T cells, induction of IL-17+ γδ T cells, inhibition of oligodendrocyte maturation, induction of poly ADP-ribose polymerase-1 (PARP-1)-dependent pathway in microglia, macrophages and astrocytes and inhibition of type I interferons expression. The contribution of TLR2-related immunopathological responses in the MS and EAE pathogenesis and its possible targeting as promising therapeutic potentials are considered in this review.

BACKGROUND/AIMS Toll-like receptors (TLRs), particularly TLR2 and TLR4, take part in elicitation of immune responses against Helicobacter pylori (H. pylori). This study aimed to investigate the relationship between single nucleotide polymorphisms (SNP) rs3804099 in the TLR2 gene and rs4986790 in the TLR4 gene with H. pylori infection and peptic ulcer (PU). MATERIALS AND METHODS Blood specimens were obtained from 350 individuals, including 100 H. pylori-infected patients with PU, 125 H. pylori-infected asymptomatic subjects (AS), and 125 non-infected healthy subjects (NHS). The DNA was extracted, and the SNPs were determined using ARMS-PCR method. RESULTS The frequency of CT genotype at TLR2 SNP rs3804099 in both the PU and AS groups was significantly higher than in the NHS group (p

Background Resistance to antimonials is a fundamental determinant of treatment failure in anthroponotic cutaneous leishmaniasis (ACL). Detection of reliable molecular markers to distinguish unresponsive and responsive parasites is critical for consolidating strategies to monitor drug efficacy. Methods We analysed the expression of five major antimony resistance-associated genes that is aquaglyceroporin1 (AQP1), γ-glutamylcysteine synthetase (γ-GCS), multidrug resistance protein A (MRPA), trypanothione reductase (TR) and thiol-dependent reductase 1 (TDR1), in unresponsive and responsive Leishmania tropica field isolates by quantitative real-time PCR in comparison with sensitive and resistant reference strains. Results Gene expression analysis showed the down-regulation of AQP1, γ-GCS and TDR1 by a factor of 1.9, 1.7 and 3.55, respectively, in unresponsive isolates vs. responsive ones. The average RNA expression level of MRPA increased by a factor of 1.9 in the unresponsive group. Isolates exhibited a strong positive linear correlation between gene expression of AQP1 and γ-GCS. A negative correlation between the AQP1 and γ-GCS expression level and lesion duration in responsive patients indicated the potential role in diagnosing drug-unresponsive parasites in endemic areas of ACL. Conclusion In cases of inconclusive outcomes of resistance tests in clinical isolates, expression analysis of a set of influential genes can be beneficial to identify distinctive biomarkers between antimony-unresponsive and responsive parasites.

Recently the role of indole and pyran rings in carcinogenesis has been well studied. Here we studied the effects and the possible mechanisms of the action of basal indole (I3A) and its novel indole derivative (C19H15F3N2O) on inhibition of proliferation cells in acute promyelocytic leukemia NB4 cell line by examining the expression of cell cycle genes. We treated NB4 cells with concentration of C19H15F3N2O for 24-72 h. The MTT and PI/Annexin V examinations were employed for assessment of the proliferation and apoptosis of NB4 cells. Both of Cyclin D and P21 were detected by the Real-time PCR. The western blotting analysis was also performed to show the protein levels for P21. A difference was regarded significant if p-value was less than 0.05. MTT assay showed that 15.12-1000 µg/mL C19H15F3N2O caused a time and concentration-dependent inhibition of NB4 cell proliferation. Exposure to higher concentrations of C19H15F3N2O resulted in significantly increased apoptosis rate in NB4 cells. RT PCR showed that C19H15F3N2O has up-regulated the expression of P21 and down-regulated the expression of Cyclin D. Western blotting experiments also demonstrated that the P21 expression in C19H15F3N2O treated cells has significantly increased, where compared with either untreated control cells or I3A treated cells. This newly (C19H15F3N2O) was able to inhibit NB4 cells proliferation and causes apoptosis of these cells more than I3A, and these effects are probably facilitated via cell cycle arrest. C19H15F3N2O might probably be introduced as a promising organic therapeutic reagent against APL.

Background Chemokines facilitate the leukocytes infiltration into the central nervous system (CNS) which is an essential step in the pathogenesis of multiple sclerosis. Ginger has also a broad anti-inflammatory properties. The aim was to evaluate the effects of ginger extract on the expression of CCL20 and CCL22 and their receptors (CCR6 and CCR4, respectively) in experimental autoimmune encephalomyelitis (EAE). Material and Methods Female C57BL/6 mice used for EAE induction by immunization with myelin oligodendroglial glycoprotein. Then, the EAE mice were treated with PBS or ginger extract, from day +3 to +30. At day 31, mice were scarified and the expression of CCL20 and CCL22 and their receptors in the spinal cord measured using real time-PCR. Results The expression of CCL20, CCL22 and CCR4 in the spinal cord of PBS-administrated EAE mice was significantly higher than healthy group (P Conclusion Treatment of EAE mice with ginger extract down-regulate the expression of CCL20 and CCL22 and their receptors in EAE mice. The possible therapeutic potential of ginger for treatment of MS can be considered in future investigations.

Toll like receptors (TLRs) are an essential subset of pathogen recognition receptors (PRRs) which identify the microbial components and contribute in the regulation of innate and adaptive immune responses against the infectious agents. The TLRs, especially TLR2, TLR4, TLR5 and TLR9, participate in the induction of immune response against H. pylori. TLR2 is expressed on a number of immune and non-immune cells and recognizes a vast broad of microbial components due to its potential to form heterodimers with other TLRs, including TLR1, TLR6 and TLR10. A number of H. pylori-related molecules may contribute to TLR2-dependent responses, including HP-LPS, HP-HSP60 and HP-NAP. TLR2 plays a pivotal role in regulation of immune response to H. pylori through activation of NF-κB and induction of cytokine expression in epithelial cells, monocytes/macrophages, dendritic cells, neutrophils and B cells. The TLR2-related immune response that is induced by H. pylori-derived components may play an important role regarding the outcome of the infection toward bacterial elimination, persistence or pathological reactions. The immunomodulatory and immunoregulatory roles of TLR2 during H. pylori infection were considered in this review. TLR2 could be considered as an interesting therapeutic target for treatment of H. pylori-related diseases.

The regulatory T (Treg) cells play a major role in the control of the autoimmunity and inflammation, and IL-35 has been described as an immunosuppressive cytokine that is mainly produced by CD4+ FOXP3+ Treg cells. The aim of this study was to evaluate the serum levels of IL-35 and a single nucleotide polymorphism (SNP), rs3761548, in FOXP3 gene in patients with multiple sclerosis. The blood samples were collected from 140 multiple sclerosis (MS) patients (including 51 untreated and 89 treated patients) and 140 healthy subjects as a control group. The serum levels of IL-35 were measured by ELISA. The DNA was analyzed for SNP rs3761548 in FOXP3 gene using SSP-PCR. There was no significant difference between untreated MS patients and control group regarding the mean serum levels of IL-35, although this parameter was higher in untreated patients. However, the mean serum level of IL-35 in treated MS patients was significantly higher than that in the control group (P

Chemokines play an important role in the autoimmune diseases. The aim of this study was to investigate the levels of CCL20 and a polymorphism [-786C > T (rs6749704)] in the chemokine gene in patients with multiple sclerosis (MS). The blood samples were collected from 135 MS patients and 135 healthy subjects as a control group. The patients have relapsing-remitting (RRMS; n = 65), primary progressive (PPMS; n = 47), secondary progressive (SPMS; n = 35) or progressive relapsing (PRMS; n = 14) patterns. The serum levels of CCL20 were measured by ELISA. The DNA was analyzed for CCL20 polymorphism using PCR–RLFP. The mean serum levels of CCL20 in the MS group were significantly higher than in the healthy group (P

IL-33 has powerful immunoregulatory activities such as reinforcement of Th2 cell responses. The aim was to assess the circulating IL-33 levels and IL-33 rs1929992 polymorphism in H. pylori-infected peptic ulcer (PU) patients and asymptomatic (AS) subjects. Blood samples were obtained from 100 PU patients, 100 AS subjects and 100 uninfected individuals. Circulating IL-33 levels were detected by ELISA. After DNA extraction, the IL-33 rs1929992 polymorphism was determined using PCR-RFLP method. Serum IL-33 quantities were significantly lower in PU patients compared with AS and uninfected groups. IL-33 levels were higher in AS subjects compared with uninfected group. In PU, AS and uninfected groups, IL-33 levels were significantly higher in women than men. In PU and AS groups, the CagA+ H. pylori-infected subjects exhibit higher IL-33 levels compared with carriers of CagA− H. pylori strains. In PU patients, the frequency of genotype GG and allele G at IL-33 rs1929992 was significantly higher compared with all healthy subjects (AS + uninfected groups). The presence of genotypes GG and AG, and allele G in rs1929992 conferred greater risk for PU. In whole H. pylori-infected population (PU + AS groups), IL-33 levels in individuals with genotype AA or allele A at rs1929992 were higher than subjects with GG genotype or allele G. The reduced IL-33 production could contribute to the PU development during H. pylori infection. The IL-33 levels may be affected by individual gender, rs1929992 polymorphism, and the CagA status of bacteria. The rs1929992-related GG genotype and G allele may be associated with PU development.

Objectives: H. pylori infection has been associated with some autoimmune disorders. The aim of this study was to evaluate the serum concentrations of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected peptic ulcer patients, H. pylori-infected asymptomatic carriers and a healthy control group.Methods: A Total of 100 H. pylori-infected peptic ulcer patients, 65 asymptomatic carriers and 30 healthy H. pylori-negative subjects (as a control group) were enrolled into study. Serum samples of participants tested for the levels of rheumatoid factor and anti-nuclear antibodies by use of ELISA.Results: The mean serum levels of rheumatoid factor and anti-nuclear antibodies in peptic ulcer group was significantly higher in comparison to the control group (p

Background: The imbalance in the T helper (Th) 1/Th2 and Th1/T regulatory (Treg) cells-related immune responses plays a key role in pathogenesis of allergic asthma. Objectives: The aim of this study was to evaluate the eects of CPG-Oligodeoxynucleotide (CPG-ODN), Monophosphoryl Lipid A (MPLA) and Bacillus Calmette-Guerin (BCG) on the ratio of Th1/Th2 and Th1/Treg cells-related parameters in an animal model of asthma. Methods: This was an experimental study in which female BALB/c mice were divided to five groups and then immunized Subcuta- neously (SC) with the allergen Dermatophagoides pteronyssinus 2 (Derp2) on days 1, 15 and 22. Three groups of mice were consid- ered as test groups and pre-treated SC with CPG, CPG + MPLA or CPG + BCG on days 0, 14 and 21. Two groups were also considered as saline-control group and Derp2-sensitized control group that were administrated only saline or allergen Derp2, respectively. The mice (except saline-control group) were challenged intranasally with allergen Derp2 for ten days, from days 28 to 37 of post im- munization. Blood samples were obtained from retro-orbital sinus, on days 0, 23 and 40. The serum Interleukin (IL)-4, Interferon (IFN)- , Immunoglobulin (Ig) E and IgG2a levels were measured using the enzyme linked immunosorbent assay (ELISA) technique. The blood count of Th1- and Treg cells was detected using flow cytometry. Results: At sensitization phase, the serum IFN- /IL4 ratio was significantly increased in Derp2-sensitized group pre-treated with CPG plus MPLA or CPG plus BCG as compared with Derp2-sensitized control mice (P < 0.002 and P < 0.003). The IFN- /IL4 ratio was also markedly elevated in Derp2-sensitized group pre-treated with CPG as compared with Derp2-sensitized control mice (P = 0.07). In the challenge phase, the IFN- /IL4, IgG2a/IgE and Th1/Treg ratios in Derp2-sensitized mice pre-treated with CPG plus MPLA were significantly higher than in Derp2-sensitized control mice (P < 0.003, P < 0.006 and P < 0.003, respectively). The IFN- /IL4 and Th1/Treg ratios were also significantly raised in Derp2-sensitized mice pre-treated with CPG plus BCG in comparison with Derp2- sensitized control mice (P < 0.001 and P = 0.012, respectively). In the challenge phase the Th1/Treg ratio was significantly decreased in Derp2-sensitized group pre-treated with CPG plus BCG in comparison with Derp2-sensitized mice pre-treated with CPG (P = 0.011). The Th1/Treg ratio in Derp2-sensitized group pre-treated with CPG plus MPLA was significantly higher than in Derp2-sensitized mice pre-treated with CPG plus BCG (P < 0.035). Conclusions: These results showed that BCG, MPLA and CPG improve the Th1/Th2- and Th1/Treg cells imbalances in a mouse model of asthma.

The imbalance in Th17/Treg cell-related responses plays an important role in the pathogenesis of multiple sclerosis (MS). The development of Th17- and Treg cells is regulated by specific transcription factors—RORγt and RORα—and FOXP3, respectively. The aim was to determine the expression of RORγt, RORα, and FOXP3 in peripheral blood mononuclear cells (PBMCs) from MS patients following in vitro stimulation. The PBMCs from 22 MS patients and 20 healthy subjects were cultured in the presence of 10 μg/ml MOG, 10 μg/ml PHA, or without stimulation. The PBMCs were incubated at 37 °C for 24 h, and then the messenger RNA (mRNA) expression of RORγt, RORα, and FOXP3 was determined by real-time PCR. The expression of RORγt and RORα was increased in non-stimulated, MOG-stimulated, and PHA-stimulated PBMCs from MS patients in comparison with same cultures from the healthy group (P

BACKGROUND The CXCL10 receptor, CXCR3, is preferentially expressed on Th1 and NK cells. Therefore, CXCL10 acts as a chemoattractant for these cells. OBJECTIVE The aim was to evaluate the CXCL10 levels and a single nucleotide polymorphism (SNP), rs4508917, in chemokine gene, in patients with breast cancer (BC). METHODS A total of 200 subjects including 100 women with BC and 100 healthy women were enrolled into study. The serum CXCL10 levels were measured by ELISA and the SNP rs4508917 was determined by polymerase chain reaction-restriction length polymorphism (PCR-RFLP). RESULTS The CXCL10 levels were significantly higher in patients than control group (P< 0.0001). There was also significant difference between tumor stages regarding the CXCL10 levels (P< 0.0001). The frequencies of GG genotype and G allele at rs4508917 were significantly higher in patients than controls (P< 0.0001). The CXCL10 levels were higher in patients with GG genotype whereas they were lower in healthy subjects having GG genotype as compared with those having AA genotype at rs4508917 (P< 0.001). CONCLUSION Higher CXCL10 levels in patients with BC represent that the chemokine may contributes in tumor development. The rs4508917 may play a role in the susceptibility to BC. Different association was also observed between rs4508917 and CXCL10 levels in patients with BC and healthy subjects.

Recruitment of leukocytes is one of the earliest events in the pathogenesis of ischemic heart disease (IHD) and chemokines play an important role in the migration of these cells into the inflammation sites. The aim of this study was to evaluate the CXCL10, CCL20 and CCL22 levels and the single nucleotide polymorphisms (SNPs) rs4508917, rs6749704 and rs4359426 in chemokine genes in patients with IHD to clarify any association. A total of 300 patients with IHD as having acute myocardial infarction (AMI; n=100), stable angina (SA; n=100) or unstable angina (UA; n=100) and 100 healthy subjects as a control group were enrolled to study. Serum samples from all participants were tested for the CXCL10, CCL20 and CCL22 levels by using ELISA. The SNPs were determined by polymerase chain reaction-restriction length polymorphism (PCR-RFLP) method. The mean serum concentrations of CXCL10, CCL20 and CCL22 in AMI patients (395.97±21.20Pg/mL, 108.38±10.31Pg/mL and 1852.58±205.77Pg/mL), SA patients (405.48±27.36Pg/mL, 90.20±7.69Pg/mL and 2322.04±231.23Pg/mL) and UA patients (396.69±22.79Pg/mL, 141.87±18.10Pg/mL and 2754.89±211.70Pg/mL) were significantly higher than in the healthy group (179.38±8.85Pg/mL, 51.92±4.62Pg/mL and 451.82±23.76Pg/mL, respectively; P

OBJECTIVE: The aim was to evaluate the interleukin (IL)-27 levels in Helicobacter pylori (H. pylori)-infected patients with gastric ulcer (GU) or duodenal ulcer (DU) and to determine its association with H. pylori virulence factor cytotoxin-associated gene A (CagA). METHODS: In all, 127 H. pylori infected patients (including 96 DU patients, of whom 61 were anti-CagA+ and 35 were anti-CagA-) and 31 GU patients (of whom 15 were anti-CagA+ and 16 were anti-CagA-), 60 asymptomatic (AS) carriers (of whom 30 were anti-CagA+ and 30 were anti-CagA-) and 30 healthy H. pylori-negative participants (as a control) were enrolled in the study. Serum concentrations of IL-27 were measured by the enzyme-linked immunosorbent assay method. RESULTS: The mean levels of IL-27 in the GU (44.26 ± 7.12 pg/mL) and DU patients (40.84 ± 3.90 pg/mL) was significantly higher than those observed in the AS carriers (22.06 ± 1.90 pg/mL, P

It has been reported that the immune system undergoes age and gender changes. The aim of this study was to investigate the age- and gender-dependent changes of salivary IgA and IgE levels among healthy subjects. A total of 203 healthy individuals (aged 1-70 years) were enrolled in the study. Two milliliters of saliva were collected from all participants, and salivary IgA and IgE levels were measured by the ELISA technique. Mean salivary IgA levels were significantly higher in subjects aged 11-20 years as compared to subjects aged 1-10 years (P < 0.01). Mean salivary IgA levels increased with age up to the age of 60 years, and then slightly decreased in subjects aged 61-70 years. The frequency of subjects with detectable levels of salivary IgE and mean salivary IgE levels gradually increased with age, with maximum levels being observed in the 31-40 years age group and not changing significantly thereafter. The mean levels of salivary IgA and IgE in adults were significantly higher than those observed in children (P < 0.00001 and P < 0.05, respectively). No significant differences were observed between men and women regarding both salivary immunoglobulins. These results showed age-dependent changes of the salivary IgA and IgE levels. Gender had no effect on the salivary levels of IgA and IgE.

Trichomonas vaginalis (T. vaginalis) infection leads to the synthesis of specific antibodies in the serum and local secretions. The profile of T. vaginalis-specific antibodies and T cell-mediated immune responses may influence the outcome of infection, towards parasite elimination, persistence or pathological reactions. Studies have indicated that Th1-, Th17- and Th22 cell-related cytokines may be protective or pathogenic, whereas Th2- and Treg cell-related cytokines can exert anti-inflammatory effects during T. vaginalis infection. A number of T. vaginalis-related components such as lipophosphoglycan (TvLPG), α-actinin, migration inhibitory factor (TvMIF), pyruvate:ferredoxin oxidoreductase (PFO), legumain-1 (TvLEGU-1), adhesins and cysteine proteases lead to the induction of specific antibodies. T. vaginalis has acquired several strategies to evade the humoral immune responses such as degradation of immunoglobulins by cysteine proteases, antigenic variation and killing of antibody-producing B cells. The characterization of the T. vaginalis-specific antibodies to significant immunogenic molecules and formulation of strategies to promote their induction in vaginal mucosa may reveal their potential protective effects against trichomoniasis. In this review, we discuss the current understanding of antibody and T cell-mediated immune responses to T. vaginalis and highlight novel insights into the possible role of immune responses in protection against parasite.

OBJECTIVE: It has been reported that the cytotoxin-associated gene A (cagA+) H. pylori strains induce severe gastric mucosal inflammation. The aim of this study was to investigate the association of the virulence factor CagA with IL-17 and IL-23 serum levels in duodenal ulcer (DU) patients and H. pylori-infected asymptomatic (AS) carriers. METHODS: In total, 45 H. pylori-infected DU patients were enrolled to study: 23 tested positive for the anti-CagA antibody (anti-CagA+) and 22 tested negative for the anti-CagA antibody (anti-CagA-), 30 were AS carriers (15 were anti-CagA+ and 15 were anti-CagA-) and 15 were healthy uninfected participants (as a control group). The IL-17 and IL-23 serum levels of participants were measured by enzyme-linked immunosorbent assay method. RESULTS: The mean IL-17 levels in DU patients were significantly higher than those in AS and control groups (P < 0.001 and P < 0.0001 respectively). In the DU group, the mean IL-17 levels in participants testing positive for anti-CagA (10.84 ± 5.79 pg/mL) were significantly higher than those observed in participants testing negative for anti-CagA (7.65 ± 4.74 pg/mL; P < 0.05). The mean IL-23 levels in the DU and AS groups were significantly higher than in the control group (P < 0.02 and P < 0.03 respectively) but were not significantly different in participants testing positive and negative for anti-CagA. CONCLUSION: These results showed higher IL-17 and IL-23 serum levels in H. pylori-infected participants than in the control group. In the DU group the expression of IL-17 was influenced by the CagA factor.

Objective CRP is a marker of inflammation and infection of the gastric mucosa with Helicobacter pylori, which causes an inflammatory reaction. It has been reported that CagA + H. pylori strains induce more severe gastric inflammation and are also associated with higher risks of peptic ulcer and gastric cancer. The purpose of this study was to compare serum concentrations of hs-CRP in H. pylori-infected peptic ulcer (PU) patients, H. pylori-infected asymptomatic (AS) carriers, and a healthy control group, and their association with bacterial virulence factor CagA. Material and Methods A total of 60 H. pylori-infected PU patients (30 patients were positive for anti-CagA antibody and 30 were negative for anti-CagA antibody), 53 H. pylori-infected AS carriers (25 subjects were positive for anti-CagA antibody and 28 were negative for anti-CagA antibody), and 22 healthy H. pylori-negative subjects (as a control group) were enrolled in the study. Serum concentrations of hs-CRP were measured by use of an ELISA method. Results The mean serum level of hs-CRP in all PU patients (124.9 ± 32.4 μg/dl) was significantly higher than that in all AS subjects (18.6 ± 2.6 μg/dl; P

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The receptor for CCL22 is named CCR4 that preferentially is expressed on the regulatory T cells (Treg), and accordingly, CCL22 acts as a chemoattractant for the intratumoral Treg migration. The aim of this study was to evaluate the serum CCL22 levels and a single nucleotide polymorphism (SNP) in chemokine gene, [2030 G/C (rs223818)], in patients with breast cancer. Blood samples were collected from 100 women with breast cancer before receiving chemotherapy, radiotherapy, or immunotherapy and 100 age-matched healthy women as a control group. The serum CCL22 levels were measured by ELISA. The DNA extracted and the SNP rs223818 determined by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. The mean serum CCL22 levels in patients with breast cancer (2398.5 ± 123 Pg/mL) was significantly higher in comparison to healthy control group (974.2 ± 39.9 Pg/mL; P

Low-dose vaccination has been proposed as a cost-saving strategy to implement mass vaccination of neonates with hepatitis B (HB) vaccine, world-wide, particularly in developing countries. The effectiveness of low vaccine doses, however, needs to be evaluated and verified in newborns from different ethnic backgrounds. In this study, a recombinant HB vaccine (Heberbiovac) was administered in three different doses, including the standard 10 microg together with 5 and 2.5 microg to three groups of healthy Iranian neonates. Each group, consisting of 230-260 subjects, received triple doses of vaccine given i.m. at 0, 1.5 and 9 month intervals. Serum samples were collected 2-4 weeks after completion of vaccination, and anti-HBs antibody was quantitated by a sandwich ELISA. Seroprotection (anti-HBs>10 IU/L) was detected in 92, 97.4 and 96.1% of 2.5, 5 and 10 microg vaccine dose recipients, with geometric mean titer (GMT) of 4502, 5824 and 6104 IU/L, respectively. No significant differences were observed in seroprotection rate and GMT between the 10 and 5 microg dose recipients. Both parameters, however, were significantly lower in neonates vaccinated with a 2.5 microg vaccine dose (P