Celastrol pretreatment attenuates concanavalin A‐induced hepatitis in mice by suppressing interleukin‐6/STAT3‐interleukin‐17 signaling

作者：Dingwu Li, Jianing Chen, Bingru Lin, Yanjun Guo, J. Pan, Chaohui Yu, Xingyong Wan · 发表于：Journal of Gastroenterology and Hepatology · 年份：2023 · DOI：10.1111/jgh.16183 · 被引用次数：13 · 研究领域：Natural Compounds in Disease Treatment、Autoimmune and Inflammatory Disorders Research、Myeloproliferative Neoplasms: Diagnosis and Treatment

Abstract Background and Aim Celastrol is extracted from Tripterygium wilfordii Hook F. It has been reported to have protective effects against various liver diseases and immune regulation of autoimmune diseases. However, little is known about whether celastrol protects against immune‐mediated hepatitis. This study aimed to investigate the effect of celastrol on liver injury induced by concanavalin A (ConA) and the potential mechanisms. Methods Intravenous administration of ConA was applied to induce acute liver injury in mice with or without pretreatment of celastrol. The effects of celastrol on ConA‐induced liver injury were further demonstrated by biochemical and histopathological assessments, immunoblotting, and flow cytometry analysis. Results Both biochemical and histopathological observations showed that pretreatment of celastrol significantly ameliorated liver injury induced by ConA. Moreover, the hepatocyte apoptosis and inflammatory responses induced by ConA were also improved in celastrol‐pretreated mice. Further studies revealed that these improvements were characterized as the celastrol‐mediated suppression of total interleukin (IL)‐17 from liver mononuclear cells in ConA‐treated mice. Flow cytometry analysis suggested that celastrol specifically decreased IL‐17 production by CD4 + T cells but not by CD8 + T cells. Fundamentally, pretreatment with celastrol inhibited both the IL‐6 produced by F4/80 + macrophages and the IL‐6 receptor on Th17 cells in the liver, wh...