ER stress activates the NLRP3 inflammasome via an UPR-independent pathway.
Details
State: Public
Version: author
Serval ID
serval:BIB_B8334B683F4E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
ER stress activates the NLRP3 inflammasome via an UPR-independent pathway.
Journal
Cell Death and Disease
ISSN
2041-4889 (Electronic)
Publication state
Published
Issued date
2012
Volume
3
Pages
e261
Language
english
Abstract
Uncontrolled endoplasmic reticulum (ER) stress responses are proposed to contribute to the pathology of chronic inflammatory diseases such as type 2 diabetes or atherosclerosis. However, the connection between ER stress and inflammation remains largely unexplored. Here, we show that ER stress causes activation of the NLRP3 inflammasome, with subsequent release of the pro-inflammatory cytokine interleukin-1β. This ER-triggered proinflammatory signal shares the same requirement for reactive oxygen species production and potassium efflux compared with other known NLRP3 inflammasome activators, but is independent of the classical unfolded protein response (UPR). We thus propose that the NLRP3 inflammasome senses and responds to ER stress downstream of a previously uncharacterized ER stress response signaling pathway distinct from the UPR, thus providing mechanistic insight to the link between ER stress and chronic inflammatory diseases.
Keywords
Animals, Carrier Proteins/genetics, Carrier Proteins/metabolism, Cell Differentiation/drug effects, Cell Line, Endoplasmic Reticulum Stress, Gene Expression/drug effects, Humans, Inflammasomes/immunology, Inflammasomes/metabolism, Inflammation/immunology, Inflammation/metabolism, Interleukin-1beta/biosynthesis, Interleukin-1beta/immunology, Lentivirus, Mice, Mice, Knockout, Potassium/metabolism, RNA, Small Interfering/genetics, Reactive Oxygen Species/metabolism, Signal Transduction/drug effects, Tetradecanoylphorbol Acetate/pharmacology, Tunicamycin/pharmacology, Unfolded Protein Response
Pubmed
Web of science
Open Access
Yes
Create date
07/12/2012 11:23
Last modification date
20/08/2019 16:26