Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Anhui 230027, China.
Immunity. 2013 Jun 27;38(6):1154-63. doi: 10.1016/j.immuni.2013.05.015.
Omega-3 fatty acids (ω-3 FAs) have potential anti-inflammatory activity in a variety of inflammatory human diseases, but the mechanisms remain poorly understood. Here we show that stimulation of macrophages with ω-3 FAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and other family members, abolished NLRP3 inflammasome activation and inhibited subsequent caspase-1 activation and IL-1β secretion. In addition, G protein-coupled receptor 120 (GPR120) and GPR40 and their downstream scaffold protein β-arrestin-2 were shown to be involved in inflammasome inhibition induced by ω-3 FAs. Importantly, ω-3 FAs also prevented NLRP3 inflammasome-dependent inflammation and metabolic disorder in a high-fat-diet-induced type 2 diabetes model. Our results reveal a mechanism through which ω-3 FAs repress inflammation and prevent inflammation-driven diseases and suggest the potential clinical use of ω-3 FAs in gout, autoinflammatory syndromes, or other NLRP3 inflammasome-driven inflammatory diseases.
ω-3 脂肪酸（ω-3 FAs）在多种人类炎症性疾病中具有潜在的抗炎活性，但作用机制仍不清楚。在这里，我们表明 ω-3 FAs（包括二十碳五烯酸（EPA）、二十二碳六烯酸（DHA）和其他家族成员）刺激巨噬细胞可消除 NLRP3 炎性体的激活，并抑制随后的半胱天冬酶-1 的激活和 IL-1β 的分泌。此外，G 蛋白偶联受体 120（GPR120）和 GPR40 及其下游支架蛋白β-arrestin-2 被证明参与了 ω-3 FAs 诱导的炎性体抑制。重要的是，ω-3 FAs 还可预防高脂肪饮食诱导的 2 型糖尿病模型中 NLRP3 炎性体依赖性炎症和代谢紊乱。我们的结果揭示了 ω-3 FAs 抑制炎症和预防炎症驱动性疾病的机制，并提示 ω-3 FAs 在痛风、自身炎症综合征或其他 NLRP3 炎性体驱动的炎症性疾病中的潜在临床应用。
