Document Detail


Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1α and sterile vascular inflammation in atherosclerosis.
MedLine Citation:
PMID:  23995233     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic inflammation is a fundamental aspect of metabolic disorders such as obesity, diabetes and cardiovascular disease. Cholesterol crystals are metabolic signals that trigger sterile inflammation in atherosclerosis, presumably by activating inflammasomes for IL-1β production. We found here that atherogenesis was mediated by IL-1α and we identified fatty acids as potent inducers of IL-1α-driven vascular inflammation. Fatty acids selectively stimulated the release of IL-1α but not of IL-1β by uncoupling mitochondrial respiration. Fatty acid-induced mitochondrial uncoupling abrogated IL-1β secretion, which deviated the cholesterol crystal-elicited response toward selective production of IL-1α. Our findings delineate a previously unknown pathway for vascular immunopathology that links the cellular response to metabolic stress with innate inflammation, and suggest that IL-1α, not IL-1β, should be targeted in patients with cardiovascular disease.
Authors:
Stefan Freigang; Franziska Ampenberger; Adrienne Weiss; Thirumala-Devi Kanneganti; Yoichiro Iwakura; Martin Hersberger; Manfred Kopf
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-09-01
Journal Detail:
Title:  Nature immunology     Volume:  14     ISSN:  1529-2916     ISO Abbreviation:  Nat. Immunol.     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-09-19     Completed Date:  2013-11-15     Revised Date:  2013-12-20    
Medline Journal Info:
Nlm Unique ID:  100941354     Medline TA:  Nat Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1045-53     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Atherosclerosis / genetics,  metabolism*,  pathology
Calcium Signaling
Dietary Fats / metabolism
Fatty Acids / metabolism*,  pharmacology
Female
Humans
Inflammasomes / metabolism*
Interleukin-1alpha / metabolism*
Interleukin-1beta / genetics,  metabolism
Ion Channels / metabolism
Macrophages / drug effects,  metabolism
Mice
Mice, Knockout
Mitochondria / drug effects,  metabolism*
Mitochondrial Proteins / metabolism
Oleic Acid / pharmacology
Plaque, Atherosclerotic / metabolism,  pathology
Vasculitis / metabolism*,  pathology
Chemical
Reg. No./Substance:
0/Dietary Fats; 0/Fatty Acids; 0/Inflammasomes; 0/Interleukin-1alpha; 0/Interleukin-1beta; 0/Ion Channels; 0/Mitochondrial Proteins; 0/mitochondrial uncoupling protein 2; 2UMI9U37CP/Oleic Acid
Comments/Corrections
Comment In:
Nat Immunol. 2013 Oct;14(10):1030-2   [PMID:  24048132 ]
Cell Metab. 2013 Nov 5;18(5):614-6   [PMID:  24206661 ]

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