Oncotarget

Research Papers:

Celastrol ameliorates inflammation through inhibition of NLRP3 inflammasome activation

Xianjun Yu _, Qun Zhao, Xixi Zhang, Haiwei Zhang, Yongbo Liu, Xiaoxia Wu, Ming Li, Xiaoming Li, Jingxuan Zhang, Xuzhi Ruan and Haibing Zhang

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:67300-67314. https://doi.org/10.18632/oncotarget.18619

Metrics: PDF 991 views  |   HTML 1464 views  |   ?  


Abstract

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

Correspondence to:

Xianjun Yu, email: xjyu_hbmu@126.com

Haibing Zhang, email: hbzhang@sibs.ac.cn

Keywords: celastrol, NLRP3, inflammasome, inflammatory disease

Received: January 12, 2017     Accepted: May 29, 2017     Published: June 27, 2017

ABSTRACT

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 18619