title: Orphan nuclear receptor Nur77 Inhibits Oxidized LDL-induced differentiation of RAW264.7 murine macrophage cell line into dendritic like cells.
abstract: BACKGROUND
  Nur77 is an orphan nuclear receptor expressed in human atheroma. In vascular cells in vitro, Nur77 expression is induced by pro-inflammatory factors, such as oxidized LDL (oxLDL).
  
  
  METHODS
  We analyze the role of Nur77 in the oxLDL-induced differentiation of macrophages into dendritic cells (DC). The murine RAW264.7 macrophage cell line was stably transfected with expression plasmids encoding either GFP or GFP fusions with either full-length Nur77 (GFP-Nur77), Nur77 lacking the DNA binding domain (GFP-Nur77-ΔDBD) or Nur77 lacking the transactivation domain (GFP-Nur77-ΔTAD).
  
  
  RESULTS
  GFP-Nur77 overexpression significantly suppressed the effect of oxLDL treatment on DC morphologic changes, expression of DC maturation markers, endocytic activity, allogeneic activation of T cell proliferation, and the activity and secretion of pro-inflammatory cytokines. Analysis of GFP-Nur77-ΔTAD and GFP-Nur77-ΔDBD indicated that the Nur77 DNA binding and transactivation domains were both required for this effect. GFP-Nur77-ΔDBD consistently had the opposite effect to GFP-Nur77, increasing DC-type differentiation in all assays. Interestingly, GFP-Nur77-ΔDBD protein was cytosolic, whereas GFP-Nur77 and GFP-Nur77-ΔTAD were both nuclear.
  
  
  CONCLUSIONS
  These data show that GFP-Nur77 inhibited differentiation of oxLDL-treated macrophages into DC. The effects of Nur77 on the macrophage phenotype may involve changes in its subcellular distribution.
authors.affiliation: Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, People's Republic of China. iam565@126.com.
authors.forename: Liu-Hua
authors.initials: LH
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, People's Republic of China. 502694441@qq.COM.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, People's Republic of China. jsx111@yahoo.com.cn.
authors.forename: Shu-Xuan
authors.initials: SX
authors.lastname: Jin
authors.affiliation: Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, People's Republic of China. niepeng4865@126.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Nie
authors.affiliation: Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, People's Republic of China. caizhaohua1987@126.com.
authors.forename: Zhao-Hua
authors.initials: ZH
authors.lastname: Cai
authors.affiliation: Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, People's Republic of China. qycuimingli0403@163.com.
authors.forename: Ming-Li
authors.initials: ML
authors.lastname: Cui
authors.affiliation: Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, People's Republic of China. sunshiqun1989@gmail.com.
authors.forename: Shi-Qun
authors.initials: SQ
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, People's Republic of China. rjshenlinghong@126.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, People's Republic of China. shaoqindr@126.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shao
authors.affiliation: Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, People's Republic of China. rjshenlinghong@126.com.
authors.forename: Ling-Hong
authors.initials: LH
authors.lastname: Shen
authors.affiliation: Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, People's Republic of China. rjheben@126.com.
authors.forename: Ben
authors.initials: B
authors.lastname: He
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008077:Lipoproteins, LDL / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000276:immunology*; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D008077:Lipoproteins, LDL; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; C099252:oxidized low density lipoprotein