Glucocorticoids Sensitize the Innate Immune System through Regulation of the NLRP3 Inflammasome

被引：209

作者：

Busillo, John M. ^{[1
]}

Azzam, Kathleen M. ^{[2
]}

Cidlowski, John A. ^{[1
]}

机构：

[1] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA

[2] NIEHS, Lab Resp Biol, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2011年 / 286卷 / 44期

基金：

美国国家卫生研究院;

关键词：

NALP3; INFLAMMASOME; ENDOTHELIAL-CELLS; INDUCED APOPTOSIS; OXIDATIVE STRESS; CUTTING EDGE; RECEPTOR; ACTIVATION; ATP; RELEASE; GENE;

D O I：

10.1074/jbc.M111.275370

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：

Glucocorticoids have long been recognized as powerful anti-inflammatory compounds that are one of the most widely prescribed classes of drugs in the world. However, their role in the regulation of innate immunity is not well understood. We sought to examine the effects of glucocorticoids on the NOD-like receptors (NLRs), a central component of the inflammasome and innate immunity. Surprisingly, we show that glucocorticoids induce both NLRP3 messenger RNA and protein, which is a critical component of the inflammasome. The glucocorticoid-dependent induction of NLRP3 sensitizes the cells to extracellular ATP and significantly enhances the ATP-mediated release of proinflammatory molecules, including mature IL-1 beta, TNF-alpha, and IL-6. This effect was specific for glucocorticoids and dependent on the glucocorticoid receptor. These studies demonstrate a novel role for glucocorticoids in sensitizing the initial inflammatory response by the innate immune system.

引用

页码：38703 / 38713

页数：11

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