Chemical mitochondrial uncouplers share common inhibitory effect on NLRP3 inflammasome activation through inhibiting NFκB nuclear translocation

被引：14

作者：

Hu, Nan ^{[1
]}

Fu, Yao ^{[1
]}

Li, Wen-Feng ^{[1
]}

Yang, Xin-Rui ^{[1
]}

Cao, Ming ^{[1
]}

Li, Feng-Feng ^{[1
]}

Chen, Jia-Hui ^{[1
]}

Chen, Xu-Yang ^{[1
]}

Zhao, Hui ^{[1
]}

Sun, Zhi-Jie ^{[2
]}

Dong, De-Li ^{[1
]}

机构：

[1] Harbin Med Univ, Heilongjiang Acad Med Sci,Dept Pharmacol, Translat Med Res & Cooperat Ctr Northern China, Key Lab Cardiovasc Res,Minist Educ,Coll Pharm,Sta, Harbin, Peoples R China

[2] China Pharmaceut Univ, Dept Pharmacol, Nanjing, Peoples R China

来源：

TOXICOLOGY AND APPLIED PHARMACOLOGY | 2021年 / 414卷

基金：

中国国家自然科学基金;

关键词：

Mitochondrial Uncouplers; NLRP3; Inflammasome; IL-1; beta; Macrophages;

D O I：

10.1016/j.taap.2021.115426

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Activation of NLRP3 inflammasome is implicated in varieties of pathologies, the aim of the present study is to characterize the effect and mechanism of mitochondrial uncouplers on NLRP3 inflammasome activation by using three types of uncouplers, niclosamide, CCCP and BAM15. Niclosamide, CCCP and BAM15 inhibited LPS plus ATP-induced increases of NLRP3 protein and IL-1 beta mRNA levels in RAW264.7 macrophages and THP-1 derived macrophages. Niclosamide, CCCP and BAM15 inhibited LPS plus ATP-induced increase of NF kappa B (P65) phosphorylation, and inhibited NF kappa B (P65) nuclear translocation in RAW264.7 macrophages. Niclosamide and BAM15 inhibited LPS-induced increase of I kappa B alpha phosphorylation in RAW264.7 macrophages, and the inhibitory effect was dependent on increased intracellular [Ca2+](i); however, CCCP showed no significant effect on I kappa B alpha phosphorylation in RAW264.7 macrophages stimulated with LPS. In conclusion, chemical mitochondrial uncouplers niclosamide, CCCP and BAM15 share common inhibitory effect on NLRP3 inflammasome activation through inhibiting NF kappa B nuclear translocation.

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页数：11

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