TY - JOUR
AB - 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.
AD - School of Clinical Medicine, School of Pharmacy and School of Basic Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan 650021, P.R. China
AU - Liu,Bei
AU - Mao,Zewei
AU - Yin,Na
AU - Gu,Qianlan
AU - Gu,Qianlan
AU - Qi,Yan
AU - Li,Xiaosi
AU - Yang,Haihao
AU - Wu,Zhao
AU - Zou,Nanting
AU - Ying,Sai
AU - Wan,Chunping
DA - 2022/10/01
DO - 10.3892/mmr.2022.12824
IS - 4
JO - Mol Med Rep
KW - MW‑9
multiple sclerosis
experimental autoimmune encephalomyelitis
T‑helper cell type 17
IL‑17A
PY - 2022
SN - 1791-2997
1791-3004
SP - 308
ST - MW‑9, a chalcones derivative bearing heterocyclic moieties, attenuates experimental autoimmune encephalomyelitis via suppressing pathogenic TH17 cells
T2 - Molecular Medicine Reports
TI - MW‑9, a chalcones derivative bearing heterocyclic moieties, attenuates experimental autoimmune encephalomyelitis via suppressing pathogenic TH17 cells
UR - https://doi.org/10.3892/mmr.2022.12824
VL - 26
ER -