title: Induction of ABCA1 and ABCG1 expression by the liver X receptor modulator cineole in macrophages.
abstract: We investigated the effect of cineole on the expression of genes related to reverse cholesterol transport and hepatic fatty acid metabolism. Cineole, a small aroma compound in teas and herbs, significantly stimulated the transactivation of liver X receptor modulator (LXR)-α and LXR-β. The mRNA and protein expression of LXRs and their target genes, including ABCA1 and ABCG1, was significantly increased in macrophages stimulated with cineole. This led to the subsequent removal of cholesterol from the cells. Interestingly, cineole showed tissue-selective LXR induction: hepatocytes stimulated with cineole showed significantly reduced expression of LXR-α and LXR-α-responsive genes, including FAS and SCD-1 (P <0.05). Accordingly, hepatocytes treated with cineole displayed reduced cellular lipid accumulation compared with control cells, as assessed by Oil Red O lipid staining and cholesterol quantification. These results suggest that cineole is a selective LXR modulator that regulates the expression of key genes in reverse cholesterol transport in macrophages without inducing lipogenesis in hepatocytes. This selective LXR modulator may have practical implications for the development of hypocholesterolemic or anti-atherosclerotic agents and also suggests.
authors.affiliation: Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713, South Korea.
authors.forename: Hee-jin
authors.initials: HJ
authors.lastname: Jun
authors.forename: Minh-Hien
authors.initials: MH
authors.lastname: Hoang
authors.forename: Siok-Koon
authors.initials: SK
authors.lastname: Yeo
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Jia
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000890:Anti-Infective Agents / Q000494:pharmacology; D003511:Cyclohexanols / Q000494:pharmacology*; D000077591:Eucalyptol; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects*; D039821:Monoterpenes / Q000494:pharmacology*; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*
chemical_list: C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D000890:Anti-Infective Agents; D003511:Cyclohexanols; D000071518:Liver X Receptors; D039821:Monoterpenes; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D000077591:Eucalyptol