NLRP3/ASC-mediated alveolar macrophage pyroptosis enhances HMGB1 secretion in acute lung injury induced by cardiopulmonary bypass

被引：179

作者：

Hou, Lei ^{[1
]}

Yang, Zhongwei ^{[1
]}

Wang, Zhankui ^{[1
]}

Zhang, Xiao ^{[1
]}

Zhao, Yanhua ^{[1
]}

Yang, Hao ^{[1
]}

Zheng, Beijie ^{[1
]}

Tian, Weitian ^{[1
]}

Wang, Shaocheng ^{[2
]}

He, Zhengyu ^{[3
]}

Wang, Xiangrui ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, Dept Anesthesiol, Shanghai 200127, Peoples R China

[2] Shanghai Tong Ji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Anesthesiol, Shanghai 200072, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, Dept Crit Care Med, Shanghai 200127, Peoples R China

来源：

LABORATORY INVESTIGATION | 2018年 / 98卷 / 08期

基金：

中国国家自然科学基金;

关键词：

ISCHEMIA-REPERFUSION INJURY; GROUP BOX 1; LIVER ISCHEMIA/REPERFUSION INJURY; NLRP3 INFLAMMASOME ACTIVATION; SPECK-LIKE PROTEIN; CELL-DEATH; CASPASE-1; ACTIVATION; SIGNALING PATHWAY; RECEPTOR; INFECTION;

D O I：

10.1038/s41374-018-0073-0

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

Our previous study showed that high levels of HMGB1 existed in rats following cardiopulmonary bypass (CPB)-induced acute lung injury (ALI) and neutralization of high-mobility group box 1(HMGB1) reduced CPB-induced ALI. However, the mechanism by which CPB increases HMGB1 secretion is unclear. Recent studies have shown that inflammasome-mediated cell pyroptosis promotes HMGB1 secretion. This study aimed to investigate the relationship between inflammasome-mediated pyroptosis and HMGB1 in CPB-related ALI. We employed oxygen-glucose deprivation (OGD)-induced alveolar macrophage (AM) NR8383 pyroptosis to measure HMGB1 secretion. We found that OGD significantly increased the levels of caspase-1 cleaved p10, IL-1 beta and ASC expression, caspase-1 activity and the frequency of pyroptotic AM, and promoted the cytoplasm transportation and secretion of HMGB1, which were significantly mitigated by ASC silencing or pretreatment with glyburide (a Nlrp3 inhibitor) in AM. CPB also increased the expression levels of Nlrp3, ASC, caspase-1 P10, and IL-1 beta, and the percentages of AM pyroptosis in the lungs of experimental rats accompanied by increased levels of serum and bronchoalveolar lavage fluid (BALF) HMGB1. Treatment with glyburide significantly mitigated the CPB-increased ASC, caspase-1 p10 and IL-1 beta expression, and the percentages of AM pyroptosis in the lungs, as well as the levels of HMGB1 in serum and BALF in rats. Therefore, our data indicated that the Nlrp3/ASC-mediated AM pyroptosis increased HMGB1 secretion in ALI induced by CPB. These findings may provide a therapeutic strategy to reduce lung injury and inflammatory responses during CPB.

引用

页码：1052 / 1064

页数：13

共 64 条

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Apoptosis-associated speck-like protein containing a caspase recruitment domain is a regulator of procaspase-1 activation [J].