Celastrol ameliorates inflammation through inhibition of NLRP3 inflammasome activation
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Xianjun Yu1,2,*, Qun Zhao1,*, Xixi Zhang1, Haiwei Zhang1, Yongbo Liu1, Xiaoxia Wu1, Ming Li1, Xiaoming Li1, Jingxuan Zhang2, Xuzhi Ruan2 and Haibing Zhang1
1Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
2Laboratory of Inflammation and Molecular Pharmacology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China
*These authors have contributed equally to this work
Xianjun Yu, email: [email protected]
Haibing Zhang, email: [email protected]
Keywords: celastrol, NLRP3, inflammasome, inflammatory disease
Received: January 12, 2017 Accepted: May 29, 2017 Published: June 27, 2017
Celastrol exhibits potential anti-inflammatory activity in a variety of inflammatory diseases, but the mechanism remains poorly understood. Activation of NLRP3 inflammasome is involved in multiple inflammatory diseases. Here, we show that celastrol abolishes the NLRP3 inflammasome activation, inhibits subsequent caspase-1 activation and IL-1β secretion both in vitro and in vivo. Notably, interruption of ASC oligomerization and autophagy activation are involved in NLRP3 inflammasome inactivation by celastrol. Importantly, in vivo results indicate that celastrol attenuates NLRP3 inflammasome-dependent inflammation diseases via autophagy-related pathway. Our results thus reveal celastrol as an inhibitor of NLRP3 inflammasome, implying the potential for clinical use of celastrol in treatment of NLRP3 inflammasome-driven inflammatory diseases.
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