Journal
BIOCHEMICAL PHARMACOLOGY
Volume 178, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2020.114090
Keywords
Celastrol; IRF3; Trex1; Interferon; Autoimmunity
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Funding
- Natural Science Foundation of Fujian Province, China [2017J01621]
- Fujian Provincial Health and Education Alliance Funds [WKJ-FJ-28]
- Innovative Research Teams Program II of Fujian Normal University in China [IRTL1703]
- Fujian Key Laboratories Funds
- Fujian Provincial Lingjun Scholarship
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Celastrol is one of most potent bioactive molecule isolated from the medicinal plant Tripterygium wilfordii (Thunder God Vine) and is well known for its potential therapeutic value against various chronic diseases including the autoimmune diseases, such as systemic lupus erythematosus and Aicardi-Goutieres syndrome, or other interferonopathies. However, the underlying mechanism of celastrol function remains unclear. Here we showed that celastrol caused inhibition of interferon regulatory factor 3 (IRF3) activation leading to the down-regulation of the interferon response triggered by cytosolic nucleic acids in vitro and in vivo. Moreover, celastrol treatment markedly ameliorates the autoimmune phenotypes including myocarditis, aberrant interferon re- sponse and autoantibody production, as well as the excessive T-cell activation in Trex1(-/- )autoimmune disease mouse model. Collectively, our results indicate that celastrol inhibits interferon response by targeting IRF3 activation and may be used as an effective treatment for interferon response-dependent autoimmune diseases.
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