雷公藤醇
PI3K/AKT/mTOR通路
蛋白激酶B
自噬
关节炎
炎性关节炎
肿瘤坏死因子α
化学
促炎细胞因子
雷公藤
细胞因子
免疫印迹
癌症研究
信号转导
医学
炎症
细胞凋亡
免疫学
病理
生物化学
替代医学
基因
作者
Junjie Yang,Jia Li,Jing Li,Ming Jing,Leiming Zhang,Mengmeng Sun,Qiaoyun Wang,Hongliu Sun,Gui‐Ge Hou,Chunhua Wang,Wenyu Xin
标识
DOI:10.1016/j.intimp.2022.109241
摘要
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder of the synovial joints. Celastrol (Cel) is a quinone-methylated triterpenoid extracted from Tripterygium wilfordii Hook F (TwHF) that has been proven to be effective in treating RA. However, the underlying molecular mechanism of celastrol in the treatment of RA remains unknown. This study explored the protective effect of celastrol against RA and the specific mechanisms of celastrol in vitro and in vivo. A chicken type II collagen (CII)-induced arthritis (CIA) mouse model was used to explore the anti-arthritic effects of celastrol, and paw swelling degree, the poly-arthritis index score and serum cytokine levels were determined. Pathological morphology was observed using hematoxylin and eosin (H&E) staining. The influences of celastrol on the proliferation of tumor necrosis factor-α (TNF-α)-induced fibroblast-like synoviocytes (FLSs) were tested by Cell Counting Kit-8 (CCK-8) assays and 5-ethynyl-2′-deoxyuridine (EdU) staining assays. The level of autophagy was detected by transmission electron microscopy (TEM). Furthermore, the PI3K/AKT/mTOR pathway and the status of autophagy in the CIA model and FLSs were also detected by western blot and immunofluorescence staining. The results showed that celastrol decreased arthritis severity and inhibited TNF-α-induced FLSs proliferation. Additionally, celastrol decreased the secretion of pro-inflammatory cytokines. Moreover, celastrol increased autophagosome levels and LC3B protein expression in TNF-α-treated FLSs. Furthermore, celastrol increased the protein expression of LC3-II and Beclin-1 and decreased the phosphorylation degree of mTOR and AKT. In conclusion, our findings confirmed that celastrol ameliorates RA via the up-regulation of autophagy by inhibiting the PI3K/AKT/mTOR axis.
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