NLRP3 Inflammasome Activation Is Essential for Paraquat-Induced Acute Lung Injury

被引：80

作者：

Liu, Zhenning ^{[1
]}

Zhao, Hongyu ^{[1
]}

Liu, Wei ^{[1
]}

Li, Tiegang ^{[1
]}

Wang, Yu ^{[1
]}

Zhao, Min ^{[1
]}

机构：

[1] China Med Univ, Shengjing Hosp, Dept Emergency Med, Shenyang 110004, Liaoning Provin, Peoples R China

来源：

INFLAMMATION | 2015年 / 38卷 / 01期

基金：

中国国家自然科学基金;

关键词：

paraquat; acute lung injury; NLRP3; inflammasome; toxicity; RECOGNITION; IMMUNITY; RECEPTOR; SHOCK;

D O I：

10.1007/s10753-014-0048-2

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The innate immune response is important in paraquat-induced acute lung injury, but the exact pathways involved are not elucidated. The objectives of this study were to determine the specific role of the NLRP3 inflammasome in the process. Acute lung injury was induced by administering paraquat (PQ) intraperitoneally. NLRP3 inflammasome including NLRP3, ASC, and caspase-1 mRNA and protein expression in lung tissue and IL-1 beta and IL-18 levels in BALF were detected at 4, 8, 24, and 72 h after PQ administration in rats. Moreover, rats were pretreated with 10, 30, and 50 mg/kg NLRP3 inflammasome blocker glybenclamide, respectively, 1 h before PQ exposure. At 72 h after PQ administration, lung histopathology changes, NLRP3, ASC, and caspase-1 protein expression, as well as secretion of cytokines including IL-1 beta and IL-18 in BALF were investigated. The NLRP3 inflammasome including NLRP3, ASC, caspase-1 expression, and cytokines IL-1 beta and IL-18 levels in PQ poisoning rats were significantly higher than that in the control group. NLRP3 inflammasome blocker glybenclamide pretreatment attenuated lung edema, inhibited the NLRP3, ASC, and caspase-1 activation, and reduced IL-1 beta and IL-18 levels in BALF. In the in vitro experiments, IL-1 beta and IL-18 secreted from RAW264.7 mouse macrophages treated with paraquat were attenuated by glybenclamide. In conclusion, paraquat can induce IL-1 beta/IL-18 secretion via NLRP3-ASC-caspase-1 pathway, and the NLRP3 inflammasome is essential for paraquat-induced acute lung injury.

引用

页码：433 / 444

页数：12

共 38 条

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