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  • Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1α and sterile vascular inflammation in atherosclerosis.

Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1α and sterile vascular inflammation in atherosclerosis.

Nature immunology (2013-09-03)
Stefan Freigang, Franziska Ampenberger, Adrienne Weiss, Thirumala-Devi Kanneganti, Yoichiro Iwakura, Martin Hersberger, Manfred Kopf
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Oleic acid, SAJ first grade, ≥70.0%
Sigma-Aldrich
Oleic acid, technical grade, 90%
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Oleic acid, natural, FCC
Supelco
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Sigma-Aldrich
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Sigma-Aldrich
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Sigma-Aldrich
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Supelco
Oleic acid, Selectophore, ≥99%