Activation of NLRP3 Inflammasome in Alveolar Macrophages Contributes to Mechanical Stretch-Induced Lung Inflammation and Injury

被引:200
|
作者
Wu, Jianbo [1 ,2 ]
Yan, Zhibo [3 ,4 ]
Schwartz, David E. [1 ]
Yu, Jingui [2 ]
Malik, Asrar B. [3 ]
Hu, Guochang [1 ,3 ]
机构
[1] Univ Illinois, Dept Anesthesiol, Coll Med, Chicago, IL 60612 USA
[2] Shandong Univ, Dept Anesthesiol, Qilu Hosp, Jinan 250012, Peoples R China
[3] Univ Illinois, Dept Pharmacol, Coll Med, Chicago, IL 60612 USA
[4] Shandong Univ, Dept Gen Surg, Qilu Hosp, Jinan 250012, Peoples R China
来源
JOURNAL OF IMMUNOLOGY | 2013年 / 190卷 / 07期
基金
美国国家卫生研究院;
关键词
OXYGEN SPECIES PRODUCTION; NALP3; INFLAMMASOME; CELL-DEATH; BARRIER DYSFUNCTION; DANGER SIGNAL; DYING CELLS; URIC-ACID; INTERLEUKIN-1-BETA; IDENTIFICATION; SECRETION;
D O I
10.4049/jimmunol.1200860
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mechanical ventilation of lungs is capable of activating the innate immune system and inducing sterile inflammatory response. The proinflammatory cytokine IL-1 beta is among the definitive markers for accurately identifying ventilator-induced lung inflammation. However, mechanisms of IL-1 beta release during mechanical ventilation are unknown. In this study, we show that cyclic stretch activates the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasomes and induces the release of IL-1 beta in mouse alveolar macrophages via caspase-1- and TLR4-dependent mechanisms. We also observed that NADPH oxidase subunit gp91(phox) was dispensable for stretch-induced cytokine production, whereas mitochondrial generation of reactive oxygen species was required for stretch-induced NLRP3 inflammasome activation and IL-1 beta release. Further, mechanical ventilation activated the NLRP3 inflammasomes in mouse alveolar macrophages and increased the production of IL-1 beta in vivo. IL-1 beta neutralization significantly reduced mechanical ventilation-induced inflammatory lung injury. These findings suggest that the alveolar macrophage NLRP3 inflammasome may sense lung alveolar stretch to induce the release of IL-1 beta and hence may contribute to the mechanism of lung inflammatory injury during mechanical ventilation. The Journal of Immunology, 2013, 190: 3590-3599.
引用
收藏
页码:3590 / 3599
页数:10
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