ClC-2 inhibition prevents macrophage foam cell formation by suppressing Nlrp3 inflammasome activation

被引：4

作者：

Ding, Wenyuan ^{[1
]}

Li, Jiamin ^{[1
]}

Wang, Lili ^{[1
]}

Zhang, Mingming ^{[1
]}

Zheng, Fei ^{[1
]}

机构：

[1] Shandong First Med Univ, Affiliated Hosp 1, Dept Cardiol, Jinan, Peoples R China

来源：

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY | 2020年 / 84卷 / 10期

关键词：

ClC-2; macrophage; foam cell formation; inflammation; Nlrp3; inflammasome; LOW-DENSITY-LIPOPROTEIN; ATHEROSCLEROSIS; MECHANISMS;

D O I：

10.1080/09168451.2020.1793294

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Macrophage foam cell formation and inflammation are a pathological hallmark of atherosclerosis. ClC-2 has been implicated in various pathological processes, including inflammation and lipid metabolic disorder. However, the functional role of ClC-2 in macrophage foam cell formation and inflammation is unclear. Here, we found that ClC-2 was dominantly expressed in macrophages of atherosclerotic plaque and increased in atherogenesis. Knockdown of ClC-2 inhibited ox-LDL -induced lipid uptake and deposition in macrophages. The increase in CD36 expression and the decrease in ABCA1 expression induced by ox-LDL were alleviated by ClC-2 downregulation. Further, ClC-2 lacking limited the ox-LDL-induced secretion of inflammatory cytokines and chemokine, and suppressed Nlrp3 inflammasome activation. Restoration of Nlrp3 expression reversed the effect of ClC-2 downregulation on macrophage lipid accumulation and inflammation. Collectively, our study demonstrates that ClC-2 knockdown ameliorates ox-LDL-induced macrophage foam cell formation and inflammation by inhibiting Nlrp3 inflammasome activation.

引用

页码：2096 / 2103

页数：8

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