Multiple sclerosis (MS) is a central nervous system autoimmune disease characterized by demyelination. Autoreactive T cells mainly interferon gamma (IFN-γ) producing T helper cells (Th1) have an important role in MS pathogenesis. Silymarin is a unique blend produced from milk thistle (Silybum marianum) plant which its imunomodulatory role has been indicated in studies. In the present study, the effects of silymarin on isolated Th1 cells were investigated in newly diagnosed MS patients and those who received betaferon. PBMCs were separated from newly diagnosed and IFN-β-treated MS patients. The Th1 cell isolation from PBMCs was performed using a human Th1 cell isolation kit. Th1 cells were cultured in the presence of silymarin (50, 100, and 150 μM for 48, 72, and 120 h). Th1 cell proliferation and CD69 expression were assessed by flow cytometry. Also, IFN-γ production and T-bet gene expression were measured by ELISA and real-time PCR respectively. In vitro cultured Th1 cells showed that silymarin suppresses Th1 cell proliferation dose and time dependently in newly diagnosed and IFN-β-treated MS patients in comparison to DMSO control. Also, CD69 expression as an early activation marker was changed after Th1 cell treatment with different doses of silymarin at different times. T-bet gene expression was significantly decreased in Th1 cells isolated from newly diagnosed and IFN-β-treated RRMS patients after treatment with silymarin compared to DMSO control. Additionally, IFN-γ production by Th1 cells was decreased after treatment silymarin in newly diagnosed patients; however, in IFN-β treated after 48-h treatment with silymarin, IFN-γ concentration was decreased at concentrations of 100 and 150 μM, and after 120 h, a significant increase was observed in the IFN-γ level at a concentration of 100 μM in comparison with DMSO. Our findings here clearly show that silymarin is an effective regulator for Th1 response in vitro condition. It not only suppresses Th1 proliferating activity but also inhibits T-bet gene expression and IFN-γ production by these cells.
Background: Multiple sclerosis has been considered as chronic inflammation of the central nervous system (CNS) and autoimmune disease .MS is most widely considered to be mediated by activation of myelin-specific T CD4+ cells as well as TH1 and TH17 cells. TH17 cell has been involved in the pathogenesis of MS in various ways. HIF-1α and RORC are required for natural differentiation of TH17 and are essential transcription factors for the evolution of TH17 cells. Numerous studies indicate that epigallocatechin gallate (EGCG) has immunomodulatory and anti-inflammatory effects. Aims: This study investigated the effect of EGCG on normoxic HIF-1α and RORC2 expression in PBMCs of MS patients. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood of new cases MS patients. The cells cultured in the presence of a different concentration of EGCG (25, 50,100μM) for 18 and 48 hours. Afterward, HIF-1α and RORC2 level expressions were measured by enzyme-linked immunosorbent assay (ELISA) and Real-Time PCR, respectively. Result: The results showed that EGCG significantly decrease RORC2 gene expression. However, EGCG did not influence the level of HIF-1α. Our present data has led us to conclude that EGCG could be considered as an anti-inflammatory agent may serving as an achievable therapeutic agent for MS.
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