Freigang, StefanStefanFreigang0000-0003-4438-7828Ampenberger, FranziskaFranziskaAmpenbergerWeiss, AdrienneAdrienneWeissKanneganti, Thirumala-DeviThirumala-DeviKannegantiIwakura, YoichiroYoichiroIwakuraHersberger, MartinMartinHersbergerKopf, ManfredManfredKopf2024-10-152024-10-152013-10https://boris-portal.unibe.ch/handle/20.500.12422/117615Chronic 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.en500 - Science::570 - Life sciences; biology600 - Technology::610 - Medicine & healtharticle10.7892/boris.458942399523310.1038/ni.2704