title: microRNA-181a represses ox-LDL-stimulated inflammatory response in dendritic cell by targeting c-Fos.
abstract: 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.
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Chaoneng
authors.initials: C
authors.lastname: Wu
authors.forename: Yunguo
authors.initials: Y
authors.lastname: Gong
authors.forename: Jie
authors.initials: J
authors.lastname: Yuan
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Aijun
authors.initials: A
authors.lastname: Sun
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D015153:Blotting, Western; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006949:Hyperlipidemias / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D039521:CD11c Antigen; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D035683:MicroRNAs; D016760:Proto-Oncogene Proteins c-fos; D014409:Tumor Necrosis Factor-alpha; C529100:mirn181 microRNA, mouse; C099252:oxidized low density lipoprotein; D016753:Interleukin-10