MW-9, a chalcones derivative bearing heterocyclic moieties, attenuates experimental autoimmune encephalomyelitis via suppressing pathogenic TH17 cells

摘要

Previous studies have indicated that MW-9, a chalcones derivative bearing heterocyclic moieties, has considerable anti-inflammatory activity in vitro. Whether MW-9 may be used to treat inflammation-based diseases, such as multiple sclerosis, remains unknown. The present study was designed to determine the effect and underlying mechanism of MW-9 in experimental autoimmune encephalomyelitis (EAE). Female C57BL/6 mice immunized with MOG(35-55) were treated with or without MW-9, then the clinical scores and other relevant parameters were investigated. Production of cytokines and specific antibodies were monitored by ELISA assays. Surface marker, Treg cell, and intracellular cytokines (IL-17A and IFN-gamma) were detected by flow cytometry, and mRNA expression in the helper-T (T-H)17 cell-related signaling pathway was examined by reverse transcription-quantitative (RT-q) PCR analysis. T(H)17 cell differentiation assay was performed. Herein, the present results demonstrated that oral administration of MW-9 reduced the severity of disease in EAE mice through slowing down infiltration process, inhibiting the demyelination, blocking anti-MOG(35-55) IgG antibody production (IgG, IgG(2a) and IgG(3)), and decreasing accumulation of CD11b(+)Gr-1(+) neutrophils from EAE mice. MW-9 treatments also led to significantly decreased IL-17A production and IL-17 expression in CD4(+) T-cells, but had no detectable influence on development of T(H)1 and T-regulatory cells ex vivo. RT-qPCR analysis showed that within the spinal cords of the mice, MW-9 blocked transcriptional expression of T(H)17-associated genes, including Il17a, Il17f, Il6 and Ccr6. In T(H)17 cell differentiation assay, MW-9 inhibited differentiation of 'naive' CD4(+) T-cells into T(H)17 cells and reduced the IL-17A production. The data demonstrated that MW-9 could attenuate EAE in part through suppressing the formation and activities of pathogenic T(H)17 cells.

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