Metabolic Signaling and Disease Program, Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Lake Nona, Orlando, FL, USA.
Circ Res. 2011 Apr 15;108(8):996-1001. doi: 10.1161/CIRCRESAHA.110.226878.
Liver X receptors (LXRs) are cholesterol-sensing nuclear receptors that are not only key regulators of lipid metabolism and transport but also suppress inflammatory signaling in macrophages through a unique mechanism of transrepression. In this brief review, we focus on the regulatory actions of LXR primarily in macrophages responding to a proatherogenic environment. LXR potentially interferes with atherosclerosis by 2 different agonist-dependent signaling pathways. The first is through promoting reverse cholesterol transportby directly activating genes of cellular cholesterol export. The second is through a general inhibitory action on proinflammatory genes where sumo-modified and agonist-bound LXR recruits negative coregulatory proteins to nuclear factor κB at immune response gene promoters through protein-protein interactions. The antiinflammatory actions of LXR may be a direct response to the proinflammatory actions recently proposed for cholesterol on inflammasome activity in the vessel wall.
肝 X 受体 (LXRs) 是胆固醇感应核受体，不仅是脂质代谢和转运的关键调节剂，而且通过独特的转录阻遏机制抑制巨噬细胞中的炎症信号。在这篇简短的综述中，我们主要关注 LXR 在巨噬细胞对动脉粥样硬化环境的反应中的调节作用。LXR 通过 2 种不同的激动剂依赖信号通路潜在地干扰动脉粥样硬化。第一种是通过直接激活细胞胆固醇外排的基因来促进胆固醇逆向转运。第二种是通过对促炎基因的普遍抑制作用，SUMO 修饰和激动剂结合的 LXR 通过蛋白-蛋白相互作用在免疫反应基因启动子处募集负性核心调节蛋白到 NF-κB。LXR 的抗炎作用可能是对最近提出的胆固醇在血管壁中对炎症小体活性的促炎作用的直接反应。
