Immunoregulatory Effects of Silymarin on Proliferation and Activation of Th1 Cells Isolated from Newly Diagnosed and IFN
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ORIGINAL ARTICLE
Immunoregulatory Effects of Silymarin on Proliferation and Activation of Th1 Cells Isolated from Newly Diagnosed and IFN-ß1b-Treated MS Patients Fereshteh Navabi,1 Vahid Shaygannejad,2,3 Faezeh Abbasirad,1 Elaheh Vaez,1 Fahimeh Hosseininasab,1 Mohammad Kazemi,2 Omid Mirmosayyeb,2,4 Fereshteh Alsahebfosoul,1 and Nafiseh Esmaeil1,5
Abstract— 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 1
Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, 81744-176, Iran 2 Isfahan Neurosciences Research Center, Alzahra Hospital, Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran 3 Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 4 Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran 5 To whom correspondence should be addressed at Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, 81744-176, Iran. E-mail: [email protected]
0360-3997/18/0000-0001/0 # 2018 Springer Science+Business Media, LLC, part of Springer Nature
Navabi, Shaygannejad, Abbasi-rad, Vaez, Hosseininasab, Kazemi, Mirmosayye, Alsahebfosoul, and Esmaeil IFN-γ level at a concentration of 100 μM in comparison with DMSO. Our findings here clearly show that si
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