Aihong Zhang; Quanhui Zheng
Abstract
Background: Understanding the effects of epigenetic factors on the pathogenesis of rheumatoid arthritis (RA) is important for the early diagnosis and therapeutic intervention of this disease. MicroRNA-150 (miR-150) exerts an important influence on the development and function of lymphocytes. However, ...
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Background: Understanding the effects of epigenetic factors on the pathogenesis of rheumatoid arthritis (RA) is important for the early diagnosis and therapeutic intervention of this disease. MicroRNA-150 (miR-150) exerts an important influence on the development and function of lymphocytes. However, the role of miR-150 in the pathogenesis of RA remains unclear.Objective: To explore the role of miR-150 in the pathogenesis of RA and the related immune mechanism.Methods: In this study, we used miR-150 knock-out (miR-150KO) and created animal models of RA. Flow cytometry, immunohistochemistry, and real-time RT-PCR were employed to assess the frequency of T cell subsets and cytokines expression.Results: Compared to wild-type (WT) mice, the onset of RA was postponed and the incidence of RA was reduced in miR-150KO mice. The expression of IL-4 and IFN-γ significantly increased while the expression of IL-17 decreased significantly in NKT and CD4+ T cells of KO mice compared to that of WT mice after RA induction. In addition, the expression of IL-4 and IFN-γ increased while the expression of IL-17 decreased significantly in the joint tissues of KO mice compared to that of WT mice. Furthermore, the mRNA expression of TNF-α and IL-17 decreased significantly in the synovial fluid cells of KO mice compared to that of the WT mice after RA induction.Conclusion: MiR-150 deficiency decreases the expression of IL-17 in T cells and joint tissues, and alleviates the occurrence and progression of RA in mice.
Yan Jiang; Linqiao Li; Qilu Pan; Xiaojing Du; Qian Han; Feixiang Ling; Rou Li; Lin Mai; Jianwei Huang; Shuyuan Chu; Libing Ma
Abstract
Background: Little is known about MBD2’s epigenetic regulation in the immune pathogenesis of CD4+T cell differentiation.Objective: This study attempted to explore the mechanism of methyl-cpg-binding domain protein 2 (MBD2) in CD4+T cell differentiation stimulated by environmental allergen ovalbumin ...
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Background: Little is known about MBD2’s epigenetic regulation in the immune pathogenesis of CD4+T cell differentiation.Objective: This study attempted to explore the mechanism of methyl-cpg-binding domain protein 2 (MBD2) in CD4+T cell differentiation stimulated by environmental allergen ovalbumin (OVA).Methods: Mononuclear cells were separated from the spleen tissues of male C57BL/6 mice. The OVA interfered with the differentiation of splenic mononuclear cells and CD4+T cells. The CD4+T cells were obtained by magnetic beads and identified by CD4 labeled antibody. CD4+T cells were transfected with lentivirus to silence MBD2 gene. A methylation quantification kit was used to detect 5-mC levels.Results: The purity of CD4+T cells reached 95.99% after magnetic beads sorting. Treatment with 200 μg/mL OVA stimulated the CD4+T cells differentiation to Th17 cells and promoted the secretion of IL-17. After being induced, the Th17 cell ratio increased. 5-Aza inhibited the Th17 cell differentiation and the IL-17 level in a dose-dependent manner. Under the intervention of the Th17 induction and 5-Aza, MBD2 silencing inhibited the differentiation of Th17 cell, and decreased the IL-17 and 5-mC levels in the cell supernatants. MBD2 silencing reduced the scale of the Th17 cell and IL-17 levels in the OVA-treated CD4+T cells.Conclusion: MBD2 affected IL-17 and 5-mC levels by mediating the Th17 cell differentiation in splenic CD4+T cells that were interfered with 5-Aza. OVA induced Th17 differentiation and increased IL-17 levels, inhibited by MBD2 silencing.
Hong Ouyang; Jie Cheng; Jingdong Du; Huiyun Gan; Zheng Lu
Abstract
Background: T helper 17 (Th17) cells and the related cytokines, interleukin (IL)- 17 and IL-23, were proved to play pivotal roles during the development of allergic rhinitis (AR). IL-27, an anti-inflammatory cytokine, has been reported to promote the production of IL-12R and induce Th1 cell responses. ...
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Background: T helper 17 (Th17) cells and the related cytokines, interleukin (IL)- 17 and IL-23, were proved to play pivotal roles during the development of allergic rhinitis (AR). IL-27, an anti-inflammatory cytokine, has been reported to promote the production of IL-12R and induce Th1 cell responses. However, its effect on Th17 responses was not fully understood. Objective: We conducted the present research to explore the role of IL-27 in the regulation of Th17 responses in AR. Methods: Thirty confirmed AR patients and 20 controls were recruited for the study. The mRNA expression and protein levels of IL-27 were analyzed employing quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively, and their correlations with Th17 cytokines were analyzed. We utilized ELISA and qPCR to analyze the effect of IL-27 on the differentiation of Th17 cells and the production of IL-17 and IL-23 from peripheral blood mononuclear cells (PBMCs). Results: We found that the IL-27 levels in AR were downregulated and negatively related to IL-17 and IL-23 levels. The recombinant IL-27 inhibited the mRNA expression of RORγt and the protein expression of IL-17 and IL-23 in PBMCs through MEK, NF-κB, and JNK pathways. Conclusion: Our data demonstrated that IL-27 suppressed Th17 responses through MEK, NF-κB, and JNK pathways.
Mehran Ahmadi; Abdolkarim Mahrooz; Saeid Abediankenari; Nasim Hayati Roodbari
Abstract
Background: Functional single nucleotide polymorphisms in zinc transporter 8 (ZnT8) gene may be key determinants of humoral autoreactivity to ZnT8. Objective: The present study is expected to provide new information on the association of rs11558471 in ZnT8 gene with IL-17 levels and insulin resistance ...
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Background: Functional single nucleotide polymorphisms in zinc transporter 8 (ZnT8) gene may be key determinants of humoral autoreactivity to ZnT8. Objective: The present study is expected to provide new information on the association of rs11558471 in ZnT8 gene with IL-17 levels and insulin resistance in an Iranian population [a high-risk population for type 2 diabetes (T2D)]. Methods: A total of 133 patients with T2D and 128 control subjects were included. Insulin and IL-17 concentrations were determined using ELISA. Insulin and fasting glucose levels were used to determine homeostasis model assessment for insulin resistance (HOMA-IR). The genetic analyses were performed by the restricted fragment length polymorphism (RFLP) after PCR amplification. Results: The risk allele frequency of rs11558471 in this Iranian population was among the highest in different populations. In T2D patients, compared with the GG genotypes, IL-17 concentrations were significantly higher in the GA+AA group (p= 0.042). According to the genotypes of this SNP, IL-17 concentrations, fasting glucose and HOMA-IR increased with the following order:GG
Tahereh Poordast; Fateme Sadat Najib; Rasoul Baharlou; Atena Bijani; Shaghayegh Moradi Alamdarloo; Alieh Poordast
Volume 14, Issue 2 , June 2017, , Pages 172-179
Abstract
Background: Preeclampsia is a common pregnancy-specific disorder associated with significant maternal and fetal morbidity and mortality worldwide. It has been proposed that the imbalance between two CD4+ T cell subtypes, regulatory T cells (Treg) and T-helper 17 cells (Th17), is involved in the pathophysiology ...
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Background: Preeclampsia is a common pregnancy-specific disorder associated with significant maternal and fetal morbidity and mortality worldwide. It has been proposed that the imbalance between two CD4+ T cell subtypes, regulatory T cells (Treg) and T-helper 17 cells (Th17), is involved in the pathophysiology of preeclampsia. Objectives: To determine the serum levels of IL-17, IL-21, IL-23 and TGF-β in patients with preeclampsia. Methods: Blood samples were collected from 30 preeclampsia patients, 30 normotensive pregnant women and 30 healthy individuals with no history of malignancies or autoimmune disorders based on simple sampling. The serum levels of IL-17, IL-21, IL-23 and TGF-β were measured by the enzyme linked immunosorbent assay (ELISA). Results: The serum levels of IL-17 and TGF-β were significantly higher in preeclampsia patients compared to normal pregnant group and healthy individuals (p>0.0001) but interestingly, the opposite was the case for IL-23 (p=0.005). However, there were no significant differences in IL-21 between preeclampsia and normal pregnant group. Conclusions: Our results conclude that contrary to IL-21, serum levels of IL-17 and TGF-β significantly increased in preeclampsia compared to normal pregnant women, supporting an imbalance of cytokine profile in preeclamtic patients.
Abdollah Jafarzadeh; Sayyed-Vahab Azizi; Maryam Nemati; Hossain Khoramdel-Azad; Ali Shamsizadeh; Fatemeh Ayoobi; Zahra Taghipour; Zuhair-Mohammad Hassan
Volume 12, Issue 4 , December 2015, , Pages 288-301
Abstract
Background: IL-17/IL-23 axis plays an important role in the pathogenesis of several autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). The immunomodulatory properties of ginger are reported in previous studies. Objective: To evaluate the effects ...
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Background: IL-17/IL-23 axis plays an important role in the pathogenesis of several autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). The immunomodulatory properties of ginger are reported in previous studies. Objective: To evaluate the effects of ginger extract on the expression of IL-17 and IL-23 in a model of EAE. Methods: EAE was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein and then treated with PBS or ginger extracts, from day +3 to +30. At day 31, mice were scarificed and the expression of IL-17 and IL-23 mRNA in spinal cord were determined by using real time-PCR. The serum levels of cytokines were measured by ELISA. Results: The mRNA expression of IL-17, IL-23 P19 and IL-23 P40 in CNS and serum levels of IL- 17 and IL-23 were significantly higher in PBS-treated EAE mice than non-EAE group (p<0.003, p<0.001, p<0.001, p<0.05 and p<0.01, respectively). In 200 mg/kg gingertreated EAE mice the mRNA expression of IL-17, P19 and P40 in CNS and serum IL- 23 levels were significantly decreased as compared to PBS-treated EAE mice (p<0.05, p<0.001, p<0.001 and p<0.05, respectively). Moreover, 300 mg/kg ginger-treated EAE group had significantly lower expression of IL-17, P19 and P40 in CNS and lower serum IL-17 and IL-23 levels than PBS-treated EAE group (p<0.02, p<0.001, p<0.001, p<0.03 and p<0.004, respectively). Conclusion: Ginger extract reduces the expression of IL-17 and IL-23 in EAE mice. The therapeutic potential of ginger for treatment of MS could be considered in further studies.
Hadi Reihani; Maryam Rastin; Mahmoud Mahmoudi; Mohsen Ghoryani; Nafiseh Abdollahi; Nafiseh Sadat Tabasi; Shahrzad Zamani Taghizadeh Rabe; Maryam Sahebari
Volume 12, Issue 2 , June 2015, , Pages 82-93
Abstract
Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Emerging data suggests that T helper 17 (Th17) cells play a pathogenic role in SLE and the increased number of these cells correlates with disease activity. In recent years, 1α, 25-dihydroxyvitamin D3 (1,25VitD3) ...
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Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Emerging data suggests that T helper 17 (Th17) cells play a pathogenic role in SLE and the increased number of these cells correlates with disease activity. In recent years, 1α, 25-dihydroxyvitamin D3 (1,25VitD3) has been considered as an immunomodulatory factor. Objective: To investigate the effect of 1,25VitD3 on Th17 cells and on the expression of related cytokines in SLE patients. Method: Thirty SLE patients (newly diagnosed or in remission) were sampled for 10 ml whole blood to isolate peripheral blood mononuclear cells (PBMCs) using Ficoll-Hypaque density gradient centrifugation. Isolated cells were cultured in the presence and absence of 50 nM 1,25VitD3. After incubation, cells were harvested and stimulated for 4-5 hours with phorbol myristate acetate (PMA) and ionomycin in the presence of brefeldin A. IL-17 secreting cells were analyzed by flowcytometry. RNA was extracted from cultured cells, cDNA was synthesized, and the expression levels of IL-6, IL-17, IL-23 and TGF- β genes were assessed by real-time PCR. Results: The percentage of Th17 cells (CD3+ CD8- IL-17+ T cells) decreased significantly in 1,25VitD3-treated cells (3.67 ± 2.43%) compared to untreated cells (4.65 ± 2.75%) ( p=0.003). The expression of TGF- β up regulated (1.38-fold) and the expression of IL-6 (50%), IL-17 (27%) and IL-23 (64%) down regulated after 1,25VitD3 treatment. Conclusion: This study showed that 1,25VitD3 modulates Th17 related pathways in SLE patients and revealed the immunomodulatory effect of 1,25VitD3 on the Th17 mediated autoimmunity.
Fahimah Anvari; Feryal Dabagh-Gorjani; Mohammad-Sadegh SoltaniZangbar; Eskandar Kamali-Sarvestani; Zahra Malek-Hosseini; Behrouz Gharesi-Fard
Volume 12, Issue 2 , June 2015, , Pages 117-128
Abstract
Background: Pre-eclampsia (PE) is one of the most important and life-threatening pregnancy disorders that affect at least 3-5% of all pregnancies. Imbalance in helper T cell functions may play a role in predisposing to PE or severity of the disease. Elevated frequencies of Th17 cells in the peripheral ...
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Background: Pre-eclampsia (PE) is one of the most important and life-threatening pregnancy disorders that affect at least 3-5% of all pregnancies. Imbalance in helper T cell functions may play a role in predisposing to PE or severity of the disease. Elevated frequencies of Th17 cells in the peripheral blood of PE patients have been reported. Several single nucleotide polymorphisms (SNP) within IL-17 gene have been identified that may affect the IL-17 production. Objectives: To investigate the association between IL-17A (-197A/G) and IL-17F (+7488T/C) gene polymorphisms and susceptibility to PE in a group of Iranian women. Moreover, to study any correlation of the polymorphisms data with the level of IL-17, at mRNA level in the paternal and maternal parts of the placentas and also at protein level in the peripheral and placental blood samples. Methods: A group of 261 PE patients and 278 age-matched healthy women with at least two previous normal pregnancies formed the cases and controls of this study. IL-17A (-197A/G) and IL-17F (+7488T/C) polymorphisms were genotyped using PCR-RFLP method. The protein level of IL-17A was assessed in the sera of 40 PE and 40 healthy women using ELISA method and mRNA expression was also measured in placental samples of 19 PE and 19 control women using Q-PCR technique. Results: Statistical analysis indicated that there were no differences in genotype, allele or haplotype frequencies regarding the studied SNPs between cases and controls. The level of IL-17A was elevated in the placental blood and the fetal tissue at protein and mRNA levels (p< 0.009 and p<0.000, respectively) in PE as compared with the healthy women. Conclusions: The effect of IL-17 cytokine in pre-eclampsia is not due to the studied cytokine polymorphisms but local production of IL-17 might have an effect on the predisposition to the disease.
Vahid Shaygannejad; Saeed Montazeri; Azam Jamshidian; Soheil Tahani; Marjan Gharagozloo; Fereshteh Ashtari; Sahar Vesal; Seyed Javad Hasheminia; Leila Dehghani
Volume 11, Issue 2 , June 2014, , Pages 134-138
Abstract
Background: Midkine (MK) is a heparin-binding growth factor with promoting effects in inflammatory responses through enhancing leukocytes migration. Objective: To study the correlation between MK serum levels and concentration of inflammatory cytokines in Multiple Sclerosis (MS) patients. Methods: We ...
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Background: Midkine (MK) is a heparin-binding growth factor with promoting effects in inflammatory responses through enhancing leukocytes migration. Objective: To study the correlation between MK serum levels and concentration of inflammatory cytokines in Multiple Sclerosis (MS) patients. Methods: We evaluated the MK level and its relationship with inflammatory cytokines (IL-17 and IL-23) and antiinflammatory ones (IL-10 and TGF-β) in multiple sclerosis (MS) patients. The serum concentrations of MK and cytokines were assessed by ELISA in 32 MS patients in comparison with 32 healthy subjects. Results: Our data showed that the MK concentration in MS patients is lower than healthy controls (341.15 ± 40.71 Pg/ml vs. 620.15 ± 98.61 Pg/ml, respectively, p=0.015). We also observed a significant decrease in IL-10, IL-23, and TGF-β cytokine levels in MS patients. There was a significant correlation between MK and IL-23 concentrations in our study (r = +0.829, p≤0.001). Conclusion: These results confirm a role for MK in inflammatory reactions in MS.
Mojgan Mohammadi; Mohammad Javad Zahedi; Amin Reza Nikpoor; Mohammad Reza Baneshi; Mohammad Mahdi Hayatbakhsh
Volume 10, Issue 2 , June 2013, , Pages 83-92
Abstract
Background: Inflammatory bowel disease, an autoimmune disease, has two clinical manifestations including Crohn’s disease and ulcerative colitis (UC). IL-17 has been the target of intensive research in autoimmune diseases. The influence of Toll like receptor 4 (TLR-4) gene polymorphisms on IL-17 ...
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Background: Inflammatory bowel disease, an autoimmune disease, has two clinical manifestations including Crohn’s disease and ulcerative colitis (UC). IL-17 has been the target of intensive research in autoimmune diseases. The influence of Toll like receptor 4 (TLR-4) gene polymorphisms on IL-17 production has also been revealed in UC patients and tissue inflammation in mice. Objectives: To investigate the association between the TLR-4 gene polymorphisms, Asp299Gly and Thr399Ile and IL-17 serum levels with ulcerative colitis. Additionally, we aimed to study modulation effects of forenamed gene polymorphisms on IL-17 serum levels in UC patients and controls. Methods: A total of 256 healthy controls and 85 UC patients enrolled in our study. DNA was extracted and PCR-RFLP technique was employed to determine Asp299Gly and Thr399Ile polymorphisms in TLR-4 gene and IL-17 serum levels were measured by ELISA method. Results: There was no significant difference between the frequency of Asp299Gly A>G and Thr399Ile C>T in UC patients and controls. While IL-17 serum levels in UC patients were significantly higher than controls (p=0.003), no significant difference in IL-17 levels between different genotypes existed. Additionally, a significant inverse relationship was observed between hemoglobin level and IL-17 serum levels in UC patients (p=0.039). Conclusions: Increased IL-17 serum levels in our UC patients might be explained through the synergistic activity of IL-17/IL-23 axis and pro-inflammatory cytokines, causing severe clinical outcome in patients with IBD. The prolonged excretion of blood in stool driven by inflammatory process which causes iron metabolism disorder and anemia may elucidate the inverse correlation between hemoglobin and IL-17 serum levels in UC patients. Lack of association between the TLR-4 gene polymorphisms and UC in our study was consistent with the results from other Caucasian populations.
Soghra Khazardoust; Pouya Javadian; Bahram Salmanian; Farnaz Zandevakil; Fatemeh Abbasalizadeh; Shohreh Alimohamadi; Sedigheh Borna; Tooba Ghazanfari; Sedigheh Hantoushzadeh
Volume 9, Issue 3 , September 2012, , Pages 199-207
Abstract
Background: There are strong evidences suggesting the secretion of different cytokines in cervical fluid during preterm labor. Betamethasone is widely administered for several reasons in preterm conditions. Objective: To Investigate the possible effect of betamethasone on endocervical cytokine concentration ...
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Background: There are strong evidences suggesting the secretion of different cytokines in cervical fluid during preterm labor. Betamethasone is widely administered for several reasons in preterm conditions. Objective: To Investigate the possible effect of betamethasone on endocervical cytokine concentration of women at risk of preterm labor. Methods: In a randomized clinical trial of 80 prime-gravid women in preterm labor between 34 and 37 weeks of gestation, cervical fluid was collected. Endocervical concentration of inflammatory cytokines were analyzed before and 48 hours after betamethasone treatment for the evaluation of IL-8, IL-17, IFN-γ and TGF-β. Wilcoxon and Mann-Whitney tests were employed for statistical analysis. χ2 and Student’s t tests were used whenever needed. Results: All the measured cytokines showed significant changes in the betamethasone treated group. IL-17 (p=0.001), IL-8 (p=0.001), and IFN- γ (p<0.05) decreased significantly, while TGF-β had a significant increase (p<0.05). In the patients who delivered before or on the 7th day of admission, IL-17, IL-8, and IFN-γ levels were all significantly higher. However, TGF-β decreased significantly in the same samples in the betamethasone treated group (p<0.05). Conclusion: Betamethasone significantly decreases the endocervical pro-inflammatory cytokine concentrations in patients with preterm labor.
Siamak Sandoghchian Shotorbani; Yue Zhang; Samuel Essien Baidoo; Huaxi Xu; Mohammad Ahmadi
Volume 8, Issue 4 , December 2011, , Pages 209-217
Abstract
Background: IL-4 is a cytokine that induces differentiation of naive helper T cells into Th2 cells. Once activated by IL-4, Th2 cells subsequently produce additional IL-4. Objective: To examine the effect of IL-4 on IL-17 production and its effect in Collagen- Induced Arthritis (CIA) mice. Method: In ...
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Background: IL-4 is a cytokine that induces differentiation of naive helper T cells into Th2 cells. Once activated by IL-4, Th2 cells subsequently produce additional IL-4. Objective: To examine the effect of IL-4 on IL-17 production and its effect in Collagen- Induced Arthritis (CIA) mice. Method: In this study, a chicken collagen-II-induced experimental arthritis (CIA) model was used in DBA/1 mice to investigate the relationship between IL-4 and IL-17 as well as other inflammatory factors. On the 38th day after the mice were induced with CIA, the expression of IL-17 and IL-4 as well as IFN-γ and IL-13 in sera of the mice was measured by QRT-PCR and ELISA. Result: The result of QRT-PCR analysis of IL-17 and IL-4 mRNA levels in the spleen showed that IL-17 is increased significantly at the onset of CIA in the spleen (p<0.01). Meanwhile, IL-17 is generally reduced at the peak of CIA but IL-4 is increased significantly at this peak in the spleen (p<0.05) when the weight of the animal was taken into consideration. Conclusion: IL-4 can be involved in the production of IL-17 at especially the peak of CIA. These results imply that the inhibition of IL-17 may decrease the expression of IL-1β and IL-6 production which will result in the aggravation of arthritis.
