Liver x receptors in atherosclerosis and inflammation.
Liver x receptors in atherosclerosis and inflammation.
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DOI：
10.1161/circresaha.110.226878
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发表时间：
2011-04-15
影响因子：
20.1
通讯作者：
Osborne TF
中科院分区：
文献类型：
--
作者：
Im SS;Osborne TF
肝脏X受体（LXR）是胆固醇敏感核受体，其不仅是脂质代谢和转运的关键调节剂，而且还通过独特的反式阻遏机制抑制巨噬细胞中的炎症信号传导。在这篇简短的综述中，我们主要关注LXR在巨噬细胞对致动脉粥样硬化环境的调节作用。LXR可能通过两种不同的激动剂依赖性信号通路干扰动脉粥样硬化。第一种是通过直接激活细胞胆固醇输出基因来促进胆固醇逆向转运（RCT）。第二种是通过对促炎基因的一般抑制作用，其中sumo修饰的和激动剂结合的LXR通过蛋白质-蛋白质相互作用在免疫应答基因启动子处招募负共调节蛋白到NF-κB。LXR的抗炎作用可能是对最近提出的胆固醇对血管壁中炎性小体活性的促炎作用的直接响应。
Liver-X-receptors (LXRs) are cholesterol sensing nuclear receptors that are not only key regulators of lipid metabolism and transport, but they 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 two different agonist dependent signaling pathways. The first is through promoting reverse cholesterol transport (RCT) by directly activating genes of cellular cholesterol export. The second is through a general inhibitory action on pro-inflammatory genes where sumo-modified and agonist bound LXR recruits negative co-regulatory proteins to NF-κB at immune response gene promoters through protein-protein interactions. The anti-inflammatory actions of LXR may be a direct response to the pro-inflammatory actions recently proposed for cholesterol on inflammasome activity in the vessel wall.