Thioredoxin-interacting protein links oxidative stress to inflammasome activation.

Details

Serval ID
serval:BIB_E05AA44F8170
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Thioredoxin-interacting protein links oxidative stress to inflammasome activation.
Journal
Nature Immunology
Author(s)
Zhou R., Tardivel A., Thorens B., Choi I., Tschopp J.
ISSN
1529-2916[electronic], 1529-2908[linking]
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
11
Number
2
Pages
136-140
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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 1beta (IL-1beta). 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-1beta in the pathogenesis of type 2 diabetes.
Keywords
Animals, Carrier Proteins/immunology, Carrier Proteins/metabolism, Cell Line, Diabetes Mellitus, Type 2/immunology, Diabetes Mellitus, Type 2/metabolism, Enzyme-Linked Immunosorbent Assay, Glucose/metabolism, Humans, Immunoblotting, Immunoprecipitation, Inflammation/immunology, Inflammation/metabolism, Interleukin-1beta/immunology, Interleukin-1beta/metabolism, Mice, Mice, Knockout, Oxidative Stress/physiology, Signal Transduction/immunology, Thioredoxins/immunology, Thioredoxins/metabolism, Transfection
Pubmed
Web of science
Create date
27/01/2010 18:04
Last modification date
20/08/2019 16:04
Usage data