title: MiR-146a regulates IL-6 production in lipopolysaccharide-induced RAW264.7 macrophage cells by inhibiting Notch1.
abstract: Inflammatory cells, macrophages induced by lipopolysaccharide (LPS) stimulation, lead to the production of inflammatory cytokines, which are crucial to host defense. MicroRNAs are short noncoding RNAs that regulate key biological processes via suppression of gene expression at posttranscriptional levels. Recently, miR-146a has been shown to be involved in the regulation of immune and inflammatory responses. However, the role of miR-146a in LPS-induced RAW264.7 macrophage cells remains unclear. In this study, we found that the expression of miR-146a was upregulated in RAW264.7 macrophage cells in response to LPS stimulation in a dose- and time-dependent manner by one-step real-time quantitative PCR. In addition, miR-146a mimics decreased, while miR-146a inhibitor increased, the expression of inflammatory cytokine interleukin-6, but did not affect tumor necrosis factor-α expression in LPS-stimulated RAW264.7 macrophage cells. Bioinformatics analyses predict that Notch1 is a potential target of miR-146a. Moreover, miR-146a overexpression in LPS-treated RAW264.7 macrophage cells did significantly decrease Notch1 mRNA and protein levels. These results suggested that miR-146a may function as a novel feedback negative regulator to LPS-induced production of inflammatory cytokines, at least in part, via inhibiting the expression of Notch1.
authors: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, 230032, People's Republic of China.
authors: Yong
authors: Y
authors: He
authors: Xu
authors: X
authors: Sun
authors: Cheng
authors: C
authors: Huang
authors: Xiao-ran
authors: XR
authors: Long
authors: Xiang
authors: X
authors: Lin
authors: Lei
authors: L
authors: Zhang
authors: Xiong-wen
authors: XW
authors: Lv
authors: Jun
authors: J
authors: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D018716:Molecular Mimicry / Q000276:immunology; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis; D051881:Receptor, Notch1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; C497762:Notch1 protein, mouse; D012333:RNA, Messenger; D051881:Receptor, Notch1; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse
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