title: Activation of liver X receptor induces macrophage interleukin-5 expression.
abstract: 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.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Chen
authors.forename: Yajun
authors.initials: Y
authors.lastname: Duan
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Kang
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Yang
authors.forename: Meixiu
authors.initials: M
authors.lastname: Jiang
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Guangliang
authors.initials: G
authors.lastname: Li
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
authors.forename: Wenquan
authors.initials: W
authors.lastname: Hu
authors.forename: Pengzhi
authors.initials: P
authors.lastname: Dong
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Li
authors.forename: David P
authors.initials: DP
authors.lastname: Hajjar
authors.forename: Jihong
authors.initials: J
authors.lastname: Han
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics; D000071518:Liver X Receptors; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D002784:Cholesterol; D006845:Hydrocarbons, Fluorinated; D007075:Immunoglobulin M; D015848:Interleukin-5; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides