title: Statins synergize dexamethasone-induced adipocyte fatty acid binding protein expression in macrophages.
abstract: OBJECTIVE
  Macrophage adipocyte fatty acid binding protein (FABP4) plays an important role in the development of atherosclerosis. We previously reported that dexamethasone induces macrophage FABP4 mRNA expression. Statins inhibit FABP4 expression. However, it remains unknown that if statins can antagonise dexamethasone-induced macrophage FABP4 expression.
  
  
  RESULTS
  We determined the effect of co-treatment of statins and dexamethasone on macrophage FABP4 expression. Unexpectedly, statins did not block the induction of macrophage FABP4 expression by dexamethasone. In contrast, statins synergized dexamethasone-induced FABP4 expression. In vivo, pitavastatin synergized dexamethasone-induced FABP4 expression in both peritoneal macrophages and adipose tissues. Cholesterol and mevalonate, but not farnesylation and geranylgeranylation, inhibited the synergistic induction. Promoter assay disclosed a putative negative glucocorticoid regulatory element (nGRE) in FABP4 gene. Pitavastatin had little effect on expression of glucocorticoid receptor (GR). However, pitavastatin enhanced dexamethasone-mediated GR nuclear translocation but inhibited the binding of GR with nGRE.
  
  
  CONCLUSIONS
  Our study defines an important mechanism involved in the regulation of macrophage FABP4 expression by a glucocorticoid and statins.
authors.affiliation: College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Wenquan
authors.initials: W
authors.lastname: Hu
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Zhou
authors.forename: Meixiu
authors.initials: M
authors.lastname: Jiang
authors.forename: Yajun
authors.initials: Y
authors.lastname: Duan
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Li
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
authors.forename: Guo-wei
authors.initials: GW
authors.lastname: He
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.forename: David P
authors.initials: DP
authors.lastname: Hajjar
authors.forename: Jihong
authors.initials: J
authors.lastname: Han
mesh_terms: D021581:Active Transport, Cell Nucleus; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000069059:Atorvastatin; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017368:Protein Prenylation; D011758:Pyrroles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005938:Glucocorticoids; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D011804:Quinolines; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D002784:Cholesterol; D000069059:Atorvastatin; C108475:pitavastatin; D008798:Mevalonic Acid