Thioredoxin-interacting protein links oxidative stress to inflammasome activation

被引：2168

作者：

Zhou, Rongbin ^{[1
]}

Tardivel, Aubry ^{[1
]}

Thorens, Bernard ^{[2
]}

Choi, Inpyo ^{[3
]}

Tschopp, Juerg ^{[1
]}

机构：

[1] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

[2] Univ Lausanne, Ctr Integrat Genom, CH-1066 Epalinges, Switzerland

[3] Korea Res Inst Biosci & Biotechnol, Taejon, South Korea

来源：

NATURE IMMUNOLOGY | 2010年 / 11卷 / 02期

基金：

瑞士国家科学基金会;

关键词：

NALP3; INFLAMMASOME; MURAMYL DIPEPTIDE; GLUCOSE; TXNIP; IDENTIFICATION; CRYSTALS; CANCER; VDUP1;

D O I：

10.1038/ni.1831

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The NLRP3 inflammasome has a major role in regulating innate immunity. Deregulated inflammasome activity is associated with several inflammatory diseases, yet little is known about the signaling pathways that lead to its activation. Here we show that NLRP3 interacted with thioredoxin (TRX)-interacting protein (TXNIP), a protein linked to insulin resistance. Inflammasome activators such as uric acid crystals induced the dissociation of TXNIP from thioredoxin in a reactive oxygen species (ROS)-sensitive manner and allowed it to bind NLRP3. TXNIP deficiency impaired activation of the NLRP3 inflammasome and subsequent secretion of interleukin 1 beta (IL-1 beta). Akin to Txnip(-/-) mice, Nlrp3(-/-) mice showed improved glucose tolerance and insulin sensitivity. The participation of TXNIP in the NLRP3 inflammasome activation may provide a mechanistic link to the observed involvement of IL-1 beta in the pathogenesis of type 2 diabetes.

引用

页码：136 / U51

页数：6

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