title: Liver X receptor-mediated induction of cholesteryl ester transfer protein expression is selectively impaired in inflammatory macrophages.
abstract: OBJECTIVE
  Cholesteryl ester transfer protein (CETP) is a target gene for the liver X receptor (LXR). The aim of this study was to further explore this regulation in the monocyte-macrophage lineage and its modulation by lipid loading and inflammation, which are key steps in the process of atherogenesis.
  
  
  RESULTS
  Exposure of bone marrow-derived macrophages from human CETP transgenic mice to the T0901317 LXR agonist increased CETP, PLTP, and ABCA1 mRNA levels. T0901317 also markedly increased CETP mRNA levels and CETP production in human differentiated macrophages, whereas it had no effect on CETP expression in human peripheral blood monocytes. In inflammatory mouse and human macrophages, LXR-mediated CETP gene upregulation was inhibited, even though ABCA1, ABCG1, and SREBP1c inductions were maintained. The inhibition of CETP gene response to LXR agonists in inflammatory cells was independent of lipid loading (ie, oxidized LDL increased CETP production in noninflammatory macrophages with a synergistic effect of synthetic LXR agonists).
  
  
  CONCLUSIONS
  LXR-mediated induction of human CETP expression is switched on during monocyte-to-macrophage differentiation, is magnified by lipid loading, and is selectively lost in inflammatory macrophages, which suggests that inflammatory cells may not increase the circulating CETP pool on LXR agonist treatment.
authors.affiliation: INSERM UMR866, Université de Bourgogne, Dijon, France.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lakomy
authors.forename: Cédric
authors.initials: C
authors.lastname: Rébé
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Sberna
authors.forename: David
authors.initials: D
authors.lastname: Masson
authors.forename: Thomas
authors.initials: T
authors.lastname: Gautier
authors.forename: Angélique
authors.initials: A
authors.lastname: Chevriaux
authors.forename: Magalie
authors.initials: M
authors.lastname: Raveneau
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ogier
authors.forename: Anh Thoai
authors.initials: AT
authors.lastname: Nguyen
authors.forename: Philippe
authors.initials: P
authors.lastname: Gambert
authors.forename: Jacques
authors.initials: J
authors.lastname: Grober
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonnotte
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D000071518:Liver X Receptors; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009000:Monocytes / Q000473:pathology / Q000502:physiology; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D010084:Oxidation-Reduction; D049294:Phospholipid Transfer Proteins / Q000378:metabolism; D011336:Probability; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D049294:Phospholipid Transfer Proteins; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein