Activation of Liver X Receptor Induces Macrophage Interleukin-5 Expression

作者：Yuanli Chen, Yajun Duan, Yanhua Kang, Xiaoxiao Yang, Meixiu Jiang, Ling Zhang, Guang-Liang Li, Zhinan Yin, Wenquan Hu, Pengzhi Dong, Xiaoju Li, David P. Hajjar, Jihong Han · 发表于：Journal of Biological Chemistry · 年份：2012 · DOI：10.1074/jbc.m112.403394 · 被引用次数：55 · 研究领域：Cholesterol and Lipid Metabolism、Atherosclerosis and Cardiovascular Diseases、Immune Cell Function and Interaction

IL-5 stimulates production of T15/EO6 IgM antibodies that can block the uptake of oxidized low density lipoprotein by macrophages, whereas a deficiency in macrophage IL-5 expression accelerates development of atherosclerosis. Liver X receptors (LXRs) are ligand-activated transcription factors that can induce macrophage ABCA1 expression and cholesterol efflux, thereby inhibiting the development of atherosclerosis. However, it remains unknown whether additional mechanisms, such as the regulation of macrophage IL-5 expression, are related to the anti-atherogenic properties of LXR. We initially defined IL-5 expression in macrophages where the LXR ligand (T0901317) induced macrophage IL-5 protein expression and secretion. The overexpression of LXR increased, whereas its knockdown inhibited IL-5 expression. Furthermore, we found that LXR activation increased IL-5 transcripts, promoter activity, formation of an LXR·LXR-responsive element complex, and IL-5 protein stability. In vivo, we found that T0901317 increased IL-5 and total IgM levels in plasma and IL-5 expression in multiple tissues in wild type mice. In LDL receptor knock-out (LDLR(-/-)) mice, T0901317 increased IL-5 expression in the aortic root area. Taken together, our studies demonstrate that macrophage IL-5 is a target gene for LXR activation, and the induction of macrophage IL-5 expression can be related to LXR-inhibited atherosclerosis.