二烯丙基三硫化物
细胞凋亡
化学
关节炎
Wnt信号通路
活力测定
药理学
流式细胞术
免疫印迹
肿瘤坏死因子α
癌症研究
信号转导
免疫学
医学
生物化学
基因
作者
Jing Liang,Hao Ran Li,Yong Chen,Chen Zhang,Da Gui Chen,Zhangqian Liang,Yijiang Shi,Lan Ling Zhang,Lei Xin,Dong Zhao
标识
DOI:10.1016/j.intimp.2019.03.024
摘要
Diallyl Trisulfide (DATS) is an organosulfur compound extracted from garlic bulb, and exerts cardioprotective, anti-inflammatory, antioxidant, antimicrobial and anticancer effects. But its role in the pathogenesis of rheumatoid arthritis (RA) is unknown. Here we explored the influence of DATS on human fibroblast-like synoviocytes (FLS) isolated from RA patients and a mouse model of collagen-induced arthritis (CIA) and the underlying mechanism.RA-FLS were cultured and treated with different concentrations of DATS. The CCK8 assay was used to assess cell proliferation while cell apoptosis was detected by flow cytometry and western blot. The IL-8, IL-6 and IL-1β levels were determined using RT-qPCR and ELISA assay. The expression of proteins of the NF-κB and Wnt pathways were measured using western blot. Furthermore, the effect of DATS was also explored in vivo using the collagen-induced arthritis mouse model. The Th17/Treg pattern obtain from cells of spleen of collagen-induced arthritis mouse model was detected by flow cytometry.Our results showed that DATS could decrease cell viability and introduce apoptosis in RA-FLS. Furthermore, DATS significantly attenuated the production of key inflammatory cytokines induced by RA-FLS cells following treatment with tumor necrosis α (TNF-α) at a concentration of 100 μM or higher. This was due to its inhibitory effect on the NF-κB and Wnt pathway signaling in RA-FLS. Additionally, DATS decreased the production of inflammatory cytokines and regulated the immune function by restoring the balance between Th17 and Treg in CIA mouse model.In conclusion, DATS may serve as a potential curative agent for RA.
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