Parisa Maleki; Bahareh Abd-Nikfarjam; Azam Jamshidian
Abstract
Background: Concomitant signals from IL-6 and TGF-β have a central role in the Th17 cells development and differentiation, and these cells are the main promoters of demyelinating inflammation in the central nervous system (CNS) resulting in multiple sclerosis (MS). Objectives: To evaluate the simultaneous ...
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Background: Concomitant signals from IL-6 and TGF-β have a central role in the Th17 cells development and differentiation, and these cells are the main promoters of demyelinating inflammation in the central nervous system (CNS) resulting in multiple sclerosis (MS). Objectives: To evaluate the simultaneous IL-6 and TGF-β gene and their receptor protein expression in patients with Relapsing-Remitting (RR)-MS. Materials and methods: IL-6 and TGF-β mRNA and their receptor expression on the surface of CD4+T cells were evaluated using real-time PCR (RT-PCR) and flow cytometry, respectively. Results: The IL-6 mRNA expression in patients with RRMS was significantly higher than in the controls (p= 0.019). When patients who did not receive any other treatment were compared with the controls, the significant difference was substantial (p=0.006). The TGF-β mRNA expression in patients was lower than in the controls (p = 0.03). However, in patients receiving IFNβ, it increased compared with the other patients (p= 0.036). There was no difference in cytokine receptor expression between patients and the control group. Conclusion: Our data conclude an increase and decrease in mRNA expression levels of IL-6 and TGF-β in patients with RRMS, respectively. Moreover, there were no significant differences in receptor expression of either cytokines. Based on our data the balance of TGF and IL-6 appears to have a positive impact on the disease control.
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.
Forooz Peiravian; Hamid Rajaian; Afshin Samiei; Nasser Gholijani; Behrouz Gharesi-Fard; Pooneh Mokaram; Abbas Rahimi-Jaberi; Eskandar Kamali Sarvestani
Volume 13, Issue 3 , September 2016, , Pages 186-196
Abstract
Background: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and cytokines may play a role in the development of MS lesions. Objective: To determine levels of different cytokines in patients with relapsing-remitting MS (RR-MS) compared to healthy controls. Methods: Profiles ...
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Background: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system and cytokines may play a role in the development of MS lesions. Objective: To determine levels of different cytokines in patients with relapsing-remitting MS (RR-MS) compared to healthy controls. Methods: Profiles of pro-inflammatory, Th1-, Th2-, and Th17-related cytokines were compared by quantitative multiplexed ELISA-based chemiluminescent assay in 44 RR-MS and 44 healthy age- and sex-matched individuals from the same ethnicity. Results: Among pro-inflammatory cytokines, the levels of IL-6 (p=0.003), IL-8 (p=0.05) and TNF-α (p=0.002) were higher in patients than controls, though IL-4 and IL-10 as well as ΣTh2 cytokines were lower in patients (p=0.05, p=0.02 and p=0.05, respectively). After gender classification, the higher levels of IL-4 in male patients remained significant and IL-13 also showed significantly higher levels in male patients compared to male controls (p=0.003 and p=0.05, respectively). A significant negative correlation was detected between EDSS and IL-10 or ΣTh2 levels (p=0.005). In addition, IL-1α (r=0.4, p=0.05) and IFN-γ (r=0.35, p=0.05) were also directly correlated with EDSS in female patients. Conclusions: Patients with RR‑MS who are in the relapse clinical phase exhibit higher levels of pro-inflammatory cytokines and reduction in protective Th2-related cytokines.
Azam Jamshidian; Mohammad Kazemi; Vahid Shaygannejad; Mansoor Salehi
Volume 12, Issue 4 , December 2015, , Pages 311-318
Abstract
Background: Lack of sufficient information on the mechanism of plasma exchange (PE) therapy in multiple sclerosis (MS), has limited this treatment to individual patients with severe relapses who have been refractory to other treatments. This is while PE is used very successfully as a first-line standard ...
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Background: Lack of sufficient information on the mechanism of plasma exchange (PE) therapy in multiple sclerosis (MS), has limited this treatment to individual patients with severe relapses who have been refractory to other treatments. This is while PE is used very successfully as a first-line standard treatment in many other neuro-immune disorders. Recent data suggest that Treg/Th17 counterbalance may indicate the boundaries between promotion and regulation of inflammatory responses in MS and Treg/Th17 ratio may be useful as a marker for monitoring the efficiency of MS therapies. Objective: To evaluate the effect of PE on the frequency and ratio of Treg/Th17 cells through concomitant measurement of the expression levels of Treg and Th17 lineage specific transcription factors, FOXP3 and RORC2, respectively. Methods: Peripheral blood mononuclear cells of 8 relapsed MS patients were obtained before and after a complete course of PE therapy and the FOXP3 and RORC2 mRNA levels were assayed using real-time PCR approach. Results: No significant change in the expression levels of individual transcription factors existed, but a significant increase in FOXP3/RORC2 ratio (p=0.036) was observed. Conclusions: Our results suggest that PE therapy influences Treg/Th17 ratio and this maybe a mechanism by which this procedure exerts its improving effects in MS disease.
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.