Β-catenin promotes NLRP3 inflammasome activation via increasing the association between NLRP3 and ASC. (May 2020)

• Record Type: Journal Article
• Authors: Huang, Lingmin; Luo, Ruiheng; Li, Jing; Wang, Dan; Zhang, Yening; Liu, Liping; Zhang, Ningjie; Xu, Xueming; Lu, Ben; Zhao, Kai
• Is Part Of: Molecular immunology. Volume 121(2020:May)
• Page Start: 186
• Page End: 194
• Publication Date: 2020-05
• Subjects: β-catenin -- NLRP3 inflammasome -- Interleukin-1β -- XAV-939; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2020.02.017
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: β-catenin promotes NLRP3 inflammasome activation. β-catenin inhibitor XAV939 attenuated LPS-induced systemic inflammation in vivo. β-catenin barely affects the priming signal of NLRP3 inflammasome. β-catenin interacts with NLRP3 and promotes the association between NLRP3 and ASC. Abstract: NLRP3 (NOD-, LRR- and pyrin domain- containing protein 3) inflammasome is involved in diverse inflammatory diseases, so the activation of NLRP3 inflammasome needs to be tightly regulated to prevent excessive inflammation. However, the endogenous regulatory mechanisms of NLRP3 inflammasome are still less defined. Here, we report that β-catenin, which is the central mediator of the canonical Wnt/β-catenin signaling, promotes NLRP3 inflammasome activation. When we suppressed the expression of β-catenin by siRNA or pharmacological inhibitor, the NLRP3 inflammasome activation was impaired. Accordingly, β-catenin inhibitor attenuated LPS-induced systemic inflammation in vivo. Mechanistically, we found β-catenin interacted with NLRP3 and promoted the association between NLRP3 and ASC. Thus, our study revealed a novel role of β-catenin in NLRP3 inflammasome activation and suggest an endogenous crosstalk between Wnt/β-catenin signal and NLRP3 inflammasome.