Nat Immunol：发现血管硬化过程中引起血管炎症的新机制

在肥胖，糖尿病，心血管病等代谢紊乱疾病中，慢性炎症是基本症状和病因之一。胆固醇晶体是引起无菌炎症的代谢信号，而且科学家推测，该信号通过刺激IL-1β释放，激活炎症小体来介导血管炎症反应的发生，并最终导致动脉硬化。而最近，美国的研究者发现，IL-1α介导了动脉硬化的发生，还发现脂肪酸是IL-1α介导的血管炎症的诱因。脂肪酸通过解耦联线粒体上的呼吸链，阻断了IL-1β的分泌，从而阻断了胆固醇晶体引起的炎症反应，使巨噬细胞选择性释放IL-1α。这项研究发现了代谢应激引起的血管免疫病理的新机制，并且暗示着在对血管硬化病人治疗中，应该针对IL-1α而非IL-1β。【原文下载】

生物谷推荐英文摘要：

Nature immunology    doi:10.1038/ni.2704

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

Stefan Freigang1, Franziska Ampenberger1, Adrienne Weiss2, Thirumala-Devi Kanneganti3, Yoichiro Iwakura4, Martin Hersberger2 & Manfred Kopf1

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-1b production. We found here that atherogenesis was mediated by IL-1a and we identified fatty acids as potent inducers of IL-1a-driven vascular inflammation. Fatty acids selectively stimulated the release of IL-1a but not of IL-1b by uncoupling mitochondrial respiration. Fatty acid–induced mitochondrial uncoupling abrogated IL-1b secretion, which deviated the cholesterol crystal–elicited response toward selective production of IL-1a. 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-1a, not IL-1b, should be targeted in patients with cardiovascular disease.

原文下载

Freigang S, Ampenberger F, Weiss A, Kanneganti TD, Iwakura Y, Hersberger M, Kopf M.Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1α and sterile vascular inflammation in atherosclerosis.Nat Immunol. 2013 Sep 1.