Therapeutic effect of Cryptotanshinone on experimental rheumatoid arthritis through downregulating p300 mediated-STAT3 acetylation
Therapeutic effect of Cryptotanshinone on experimental rheumatoid arthritis through downregulating p300 mediated-STAT3 acetylation
复制标题
隐丹参酮通过下调 p300 介导的 STAT3 乙酰化对实验性类风湿关节炎的治疗作用
DOI：
10.1016/j.bcp.2017.05.006
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发表时间：
2017-08-15
影响因子：
5.8
通讯作者：
Liu, Liang
中科院分区：
文献类型：
--
作者：
Wang, Ying;Zhou, Chun;Liu, Liang
Background and purpose: The balance between T helper 17 (Th17) cells and regulatory T (Treg) cells, plays a critical role in rheumatoid arthritis (RA). The differentiation of Th17 cells requires the activation of STAT3, which determines the balance of Th17/Treg. Here, we investigated the therapeutic effect of Cryptotanshinone (CTS) on collagen induced mouse arthritis and explored the underlying mechanisms.Experimental approach: Arthritis was induced in DBA/1 mice with bovine collagen type II and complete Freund's adjuvant. CM was given at 20 mg kg(-1) d(-1) or 60 mg kg(-1) d(-1) by gavage for 6 weeks. The immuno-inflammation and joint destruction were evaluated and the balance of Th17/Treg was determined. STAT3 acetylation and phosphorylation were detected by western blotting, and the involvement of p300 was investigated by siRNA and plasmid overexpression.Key results: CTS at a dose of 60 mg kg(-1) d(-1) ameliorated the inflammation and joint destruction in CIA mice. It improved Th17/Treg imbalance, and inhibited both acetylation and phosphorylation of STAT3. CTS reduced p300 expression and its binding to STAT3, but increased phosphorylated AMPK. Knockdown of p300 mimicked the inhibitory effect of CTS on STAT3 acetylation and phosphorylation, which could be partially rescued by overexpression of p300-WT, but not p300-dominant negative (DN) construct.Conclusion and implications: Our study suggested that the anti-arthritis effects of CTS were attained through suppression of p300-mediated STAT3 acetylation. Our data suggest that CM might be a potential immune modulator for RA treatment. (C) 2017 Elsevier Inc. All rights reserved.
