microRNA-181a represses ox-LDL-stimulated inflammatory response in dendritic cell by targeting c-Fos

• DOI: 10.1194/jlr.m028878
• Publication Date: 2012-09-07T01:08:54Z
• Authors: Chaoneng Wu; Yunguo Gong; Jie Yuan; Wenbin Zhang; Gang Zhao; Hua Li; Aijun Sun; KaiHu; Yunzeng Zou; Junbo Ge
• Keywords: 0301 basic medicine; Blotting, Western; Enzyme-Linked Immunosorbent Assay; Hyperlipidemias; QD415-436; Biochemistry; Mice; 03 medical and health sciences; Apolipoproteins E; hyperlipidemia; Animals; dendritic cells; Research Articles; Cells, Cultured; Interleukin-6; Tumor Necrosis Factor-alpha; Dendritic Cells; Flow Cytometry; CD11c Antigen; Interleukin-10; Lipoproteins, LDL; Mice, Inbred C57BL; MicroRNAs; atherosclerosis; Proto-Oncogene Proteins c-fos

Oxidized LDL (ox-LDL) activates dendritic cells (DCs), thereby initiating inflammation responses in atherosclerosis, yet the modulatory mechanisms remain unclear. MicroRNAs (miRNAs) are important regulators for DC functions. This study evaluated the regulation by miRNAs of the ox-LDL-induced DC immune response. In CD11c(+) DCs from ApoE-deficient mice with hyperlipidemia, microRNA miR-181a was significantly up-regulated. In cultured bone marrow-derived DCs (BMDCs), ox-LDL promoted DC maturation and up-regulated miR-181a expression. Abundance of miR-181a attenuated ox-LDL-induced CD83 and CD40 expression, inhibited the secretion of interleukin (IL)-6 and TNF-α, and up-regulated IL-10, an important anti-inflammatory cytokine that was inhibited by ox-LDL. Inhibition of the endogenous miR-181a reversed the effects on CD83 and CD40 as well as the effects on IL-6 and TNF-α. The putative target genes of miR-181a were evaluated by gene ontology assessment, and the c-Fos-mediated inflammation pathway was identified. miR-181a targeted the 3' untranslated region of c-Fos mRNA by luciferase experiments. Thus, abundance of miR-181a reduced c-Fos protein, whereas inhibition of miR-181a increased c-Fos protein in BMDCs. We therefore suggest that miR-181a attenuates ox-LDL-stimulated immune inflammation responses by targeting c-Fos in DCs.