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

Abstract

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 MOG35-55 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-γ) were detected by flow cytometry, and mRNA expression in the helper-T (TH)17 cell-related signaling pathway was examined by reverse transcription-quantitative (RT-q) PCR analysis. TH17 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-MOG35-55 IgG antibody production (IgG, IgG2a and IgG3), 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 TH1 and T-regulatory cells ex vivo. RT-qPCR analysis showed that within the spinal cords of the mice, MW-9 blocked transcriptional expression of TH17-associated genes, including Il17a, Il17f, Il6 and Ccr6. In TH17 cell differentiation assay, MW-9 inhibited differentiation of ‘naïve’ CD4+ T-cells into TH17 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 TH17 cells.