Department of Hematology and Key Laboratory of Non-resolving Inflammation and Cancer of Hunan Province, the Third Xiangya Hospital, Central South University, Changsha, Hunan Province, 410000 PR China.
Department of Dermatology, the Third Xiangya Hospital, Central South University, Changsha, Hunan Province, 410000 PR China.
Mol Immunol. 2020 May;121:186-194. doi: 10.1016/j.molimm.2020.02.017. Epub 2020 Mar 31.
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.
NLRP3(NOD、LRR 和 pyrin 结构域蛋白 3)炎性小体参与多种炎症性疾病,因此需要严格调控 NLRP3 炎性小体的激活,以防止过度炎症。然而,NLRP3 炎性小体的内源性调节机制仍不明确。在这里,我们报告β-连环蛋白(canonical Wnt/β-catenin 信号的中心介质)促进 NLRP3 炎性小体的激活。当我们通过 siRNA 或药理学抑制剂抑制β-连环蛋白的表达时,NLRP3 炎性小体的激活受到损害。相应地,β-连环蛋白抑制剂减弱了 LPS 诱导的体内全身炎症。在机制上,我们发现β-连环蛋白与 NLRP3 相互作用,并促进 NLRP3 和 ASC 之间的关联。因此,我们的研究揭示了β-连环蛋白在 NLRP3 炎性小体激活中的新作用,并提示 Wnt/β-catenin 信号与 NLRP3 炎性小体之间存在内源性串扰。