β-catenin promotes NLRP3 inflammasome activation via increasing the association between NLRP3 and ASC

Lingmin Huang; Ruiheng Luo; Jing Li; Dan Wang; Yening Zhang; Liping Liu; Ningjie Zhang; Xueming Xu; Ben Lu; Kai Zhao

doi:10.1016/j.molimm.2020.02.017

β-catenin promotes NLRP3 inflammasome activation via increasing the association between NLRP3 and ASC

Mol Immunol. 2020 May:121:186-194. doi: 10.1016/j.molimm.2020.02.017. Epub 2020 Mar 31.

Authors

Lingmin Huang¹, Ruiheng Luo¹, Jing Li¹, Dan Wang², Yening Zhang¹, Liping Liu³, Ningjie Zhang⁴, Xueming Xu¹, Ben Lu⁵, Kai Zhao⁶

Affiliations

¹ 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.
² Department of Dermatology, the Third Xiangya Hospital, Central South University, Changsha, Hunan Province, 410000 PR China.
³ Department of General Surgery, the Third Xiangya Hospital, Central South University, Changsha, Hunan Province, 410000 PR China.
⁴ Department of Blood Transfusion, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, 410000 PR China.
⁵ 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; Key Laboratory of Medical Genetics, School of Biological Science and Technology, Central South University, Changsha, Hunan Province, 410000 PR China; Key Laboratory of Sepsis and Translational Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan Province, 410000 PR China; Department of Pathophysiology, School of Basic Medical Science, Jinan University, Guangzhou, Guangdong Province, 510632 PR China.
⁶ 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. Electronic address: kaizhao@csu.edu.cn.

PMID: 32244067
DOI: 10.1016/j.molimm.2020.02.017

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.

Keywords: Interleukin-1β; NLRP3 inflammasome; XAV-939; β-catenin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CARD Signaling Adaptor Proteins / immunology
CARD Signaling Adaptor Proteins / metabolism*
Disease Models, Animal
HEK293 Cells
Heterocyclic Compounds, 3-Ring / pharmacology*
Heterocyclic Compounds, 3-Ring / therapeutic use
Humans
Inflammasomes / drug effects
Inflammasomes / immunology*
Inflammation / immunology
Inflammation / prevention & control*
Injections, Intraperitoneal
Lipopolysaccharides / immunology
Macrophages / drug effects
Macrophages / immunology
Macrophages / metabolism
Male
Mice
NLR Family, Pyrin Domain-Containing 3 Protein / immunology
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
Primary Cell Culture
RNA, Small Interfering / metabolism
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Wnt Signaling Pathway / drug effects
Wnt Signaling Pathway / immunology
beta Catenin / antagonists & inhibitors
beta Catenin / genetics
beta Catenin / metabolism*

Substances

CARD Signaling Adaptor Proteins
CTNNB1 protein, mouse
Heterocyclic Compounds, 3-Ring
Inflammasomes
Lipopolysaccharides
NLR Family, Pyrin Domain-Containing 3 Protein
Nlrp3 protein, mouse
Pycard protein, mouse
RNA, Small Interfering
Recombinant Proteins
XAV939
beta Catenin