β-catenin promotes NLRP3 inflammasome activation via increasing the association between NLRP3 and ASC
β-catenin promotes NLRP3 inflammasome activation via increasing the association between NLRP3 and ASC
复制标题
β-连环蛋白通过增加 NLRP3 和 ASC 之间的关联来促进 NLRP3 炎症小体激活
DOI：
10.1016/j.molimm.2020.02.017
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发表时间：
2020-05-01
影响因子：
3.6
通讯作者：
Zhao, Kai
中科院分区：
文献类型：
--
作者：
Huang, Lingmin;Luo, Ruiheng;Zhao, Kai
NLRP 3（NOD-，LRR- and pyrin domain- containing protein 3）炎性小体参与多种炎症性疾病，因此需要严格调控NLRP 3炎性小体的活化以防止过度炎症。然而，NLRP 3炎性体的内源性调节机制仍然不太明确。在这里，我们报告，β-连环蛋白，这是典型的Wnt/β-连环蛋白信号传导的中央介质，促进NLRP 3炎性小体激活。当我们通过siRNA或药物抑制剂抑制β-catenin的表达时，NLRP 3炎性小体活化受损。因此，β-连环蛋白抑制剂在体内减弱LPS诱导的全身炎症。在机制上，我们发现β-catenin与NLRP 3相互作用，并促进NLRP 3与ASC之间的关联。因此，我们的研究揭示了β-连环蛋白在NLRP 3炎性体激活中的新作用，并表明Wnt/β-连环蛋白信号与NLRP 3炎性体之间存在内源性串扰。
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 beta-catenin, which is the central mediator of the canonical Wnt/beta-catenin signaling, promotes NLRP3 inflammasome activation. When we suppressed the expression of beta-catenin by siRNA or pharmacological inhibitor, the NLRP3 inflammasome activation was impaired. Accordingly, beta-catenin inhibitor attenuated LPS-induced systemic inflammation in vivo. Mechanistically, we found beta-catenin interacted with NLRP3 and promoted the association between NLRP3 and ASC. Thus, our study revealed a novel role of beta-catenin in NLRP3 inflammasome activation and suggest an endogenous crosstalk between Wnt/beta-catenin signal and NLRP3 inflammasome.