microRNA-181a represses ox-LDL-stimulated inflammatory response in
dendritic cell by targeting c-Fos |
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Authors: | Chaoneng Wu Yunguo Gong Jie Yuan Wenbin Zhang Gang Zhao Hua Li Aijun Sun KaiHu Yunzeng Zou Junbo Ge |
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Institution: | *Shanghai Institute of Cardiovascular
Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China;†Institute of Biomedical
Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China |
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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. |
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Keywords: | dendritic cells hyperlipidemia atherosclerosis |
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