title: Liver X receptor activation induces the uptake of cholesteryl esters from high density lipoproteins in primary human macrophages.
abstract: OBJECTIVE
  Liver X receptors (LXRs) are oxysterol-activated nuclear receptors regulating reverse cholesterol transport, in part by modulating cholesterol efflux from macrophages to apoAI and HDL via the ABCA1 and ABCG1/ABCG4 pathways. Moreover, LXR activation increases intracellular cholesterol trafficking via the induction of NPC1 and NPC2 expression. However, implication of LXRs in the selective uptake of cholesteryl esters from lipoproteins in human macrophages has never been reported.
  
  
  RESULTS
  Our results show that (1) selective CE uptake from HDL(3) is highly efficient in human monocyte-derived macrophages; (2) surprisingly, HDL(3)-CE uptake is strongly increased by LXR activation despite antiatherogenic effects of LXRs; (3) HDL(3)-CE uptake increase is not linked to SR-BI expression modulation but it is dependent of proteoglycan interactions; (4) HDL(3)-CE uptake increase is associated with increased expression and secretion of apoE and LPL, two proteins interacting with proteoglycans; (5) HDL(3)-CE uptake increase depends on the integrity of raft domains and is associated with an increased caveolin-1 expression.
  
  
  CONCLUSIONS
  Our study identifies a new role for LXRs in the control of cholesterol homeostasis in human macrophages. LXR activation results in enhanced dynamic intracellular cholesterol fluxes through an increased CE uptake from HDL and leads to an increased cholesterol availability to efflux to apoAI and HDL.
authors.affiliation: Institut Pasteur de Lille, Inserm, U545, Université de Lille 2, Faculté de Pharmacie et de Médecine Lille, Lille, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bultel
authors.forename: Lionel
authors.initials: L
authors.lastname: Helin
authors.forename: Veronique
authors.initials: V
authors.lastname: Clavey
authors.forename: Giulia
authors.initials: G
authors.lastname: Chinetti-Gbaguidi
authors.forename: Elena
authors.initials: E
authors.lastname: Rigamonti
authors.forename: Morvane
authors.initials: M
authors.lastname: Colin
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Fruchart
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Sophie
authors.initials: S
authors.lastname: Lestavel
mesh_terms: D016632:Apolipoprotein A-I / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism; D001693:Biological Transport, Active; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000819:agonists / Q000378:metabolism*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000378:metabolism*; D000071518:Liver X Receptors; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D016632:Apolipoprotein A-I; D051242:Caveolin 1; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; D006845:Hydrocarbons, Fluorinated; D008075:Lipoproteins, HDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D051122:Scavenger Receptors, Class B; D013449:Sulfonamides; C495124:SCARB1 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides