title: Identification of biological markers of liver X receptor (LXR) activation at the cell surface of human monocytes.
abstract: BACKGROUND
  Liver X receptor (LXR) α and LXR β (NR1H3 and NR1H2) are oxysterol-activated nuclear receptors involved in the control of major metabolic pathways such as cholesterol homeostasis, lipogenesis, inflammation and innate immunity. Synthetic LXR agonists are currently under development and could find applications in various fields such as cardiovascular diseases, cancer, diabetes and neurodegenerative diseases. The clinical development of LXR agonists requires the identification of biological markers for pharmacodynamic studies. In this context, monocytes represent an attractive target to monitor LXR activation. They are easily accessible cells present in peripheral blood; they express LXR α and β and respond to LXR agonist stimulation in vitro. The aim of our study was to identify cell surface markers of LXR agonists on monocytes. For this, we focused on clusters of differentiation (CD) markers because they are well characterized and accessible cell surface molecules allowing easy immuno-phenotyping.
  
  
  RESULTS
  By using microarray analysis of monocytes treated or not with an LXR agonist in vitro, we selected three CD, i.e. CD82, CD226, CD244 for further analysis by real time PCR and flow cytometry. The three CD were up-regulated by LXR agonist treatment in vitro in a time- and dose- dependent manner and this induction was LXR specific as assessed by a SiRNA or LXR antagonist strategy. By using flow cytometry, we could demonstrate that the expression of these molecules at the cell surface of monocytes was significantly increased after LXR agonist treatment.
  
  
  CONCLUSIONS
  We have identified three new cell surface markers that could be useful to monitor LXR activation. Future studies will be required to confirm the biological and diagnostic significance of the markers.
authors.affiliation: Centre de Recherche Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 866, Université de Bourgogne, Dijon, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Rébé
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Filomenko
authors.forename: Magalie
authors.initials: M
authors.lastname: Raveneau
authors.forename: Angélique
authors.initials: A
authors.lastname: Chevriaux
authors.forename: Minako
authors.initials: M
authors.lastname: Ishibashi
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Junien
authors.forename: Philippe
authors.initials: P
authors.lastname: Gambert
authors.forename: David
authors.initials: D
authors.lastname: Masson
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000494:pharmacology; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D002784:Cholesterol; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D013449:Sulfonamides; C000605210:NR1H2 protein, human; C000605213:NR1H3 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides