xav939 and Inflammation

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.

Topics: Animals; beta Catenin; CARD Signaling Adaptor Proteins; Disease Models, Animal; HEK293 Cells; Heterocyclic Compounds, 3-Ring; Humans; Inflammasomes; Inflammation; Injections, Intraperitoneal; Lipopolysaccharides; Macrophages; Male; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Primary Cell Culture; Recombinant Proteins; RNA, Small Interfering; Wnt Signaling Pathway