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7020706 
Journal Article 
Activation of liver X receptor induces macrophage interleukin-5 expression 
Chen, Y; Duan, Y; Kang, Y; Yang, X; Jiang, M; Zhang, L; Li, G; Yin, Z; Hu, W; Dong, P; Li, X; Hajjar, DP; Han, J; , 
2012 
Yes 
Journal of Biological Chemistry
ISSN: 0021-9258
EISSN: 1083-351X 
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 
BETHESDA 
287 
52 
43340-43350 
English 
23150660 
WOS:000312940800015 
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.