Orphan nuclear receptor Nur77 Inhibits Oxidized LDL-induced differentiation of RAW264.7 murine macrophage cell line into dendritic like cells

BMC Immunology

Ben He¹  Ling-hong Shen¹  Qin Shao¹  Hua Xiao¹  Shi-qun Sun¹  Ming-li Cui¹  Zhao-hua Cai¹  Peng Nie¹  Shu-xuan Jin¹  Ying Yu¹  Liu-hua Hu¹ 

[1] Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, People’s Republic of China

关键词: Dendritic cell;    Macrophage;    Oxidized LDL;    Nur77;    Nuclear receptor;   

Others  :  1089852
DOI  :  10.1186/s12865-014-0054-z

 received in 2014-04-04, accepted in 2014-11-03,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Hu et al.; licensee BioMed Central Ltd.

【 图 表 】

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