title: MiRNA-194 Regulates Palmitic Acid-Induced Toll-Like Receptor 4 Inflammatory Responses in THP-1 Cells.
abstract: There is strong evidence to suggest that inflammatory responses link obesity and diseases, and the understanding of obesity-induced inflammatory mechanisms is central to the pathogenesis of diseases such asnonalcoholic fatty liver disease(NAFLD) and atherosclerosis that are modified by obesity. Based on this, anti-inflammatory treatments become a potential therapies for obesity-related diseases like NAFLD.A critical role of toll-like receptor (TLR) and its downstream molecules such as tumor necrosis factor receptor-associated factor 6(TRAF6) has been documented in inflammatory response induced by fatty acid. TLR pathway regulation provides a new insight to controlling the inflammatory response induced by fatty acid. Taken together, our study was aimed to understand the mechanism of fatty acid-mediated inflammation and look for an effective target which can prevent the inflammatory response induced by obesity. In this study, we used the saturated fatty acid palmitic acid (PA) to activate TLR4 signal pathway in human monocyte cells THP-1 that established an intracellular inflammatory model. Followed with activated TLR4, downstream molecular TRAF6 was upregulated and ultimately induced proinflammatory cytokine production. Based on this model, we also found that PA downregulated miR-194 expression with TLR4 activation. Moreover, our results showed that key signal molecular TRAF6 is a target of miR-194, overexpression of miR-194 directly decreased TRAF6 expression and attenuated the release of proinflammatory cytokine TNF-α in PA-activated monocyte THP-1. We conclude that miR-194 negatively regulates the TLR4 signal pathway which is activated by PA through directly negative TRAF6 expression.
authors.affiliation: Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, China. 756972975@qq.com.
authors.forename: Huiqun
authors.initials: H
authors.lastname: Tian
authors.affiliation: Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, China. ctgulcq@163.com.
authors.forename: Chaoqi
authors.initials: C
authors.lastname: Liu
authors.affiliation: Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, China. 806030825@qq.com.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zou
authors.affiliation: Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, China. lezhiweiwei@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Medical College, China Three Gorges University, Yichang 443002, China. greatwall@ctgu.edu.cn.
authors.forename: Changcheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Medical College, China Three Gorges University, Yichang 443002, China. yxyydyd@126.com.
authors.forename: Ding
authors.initials: D
authors.lastname: Yuan
mesh_terms: D020413:3' Untranslated Regions; D002460:Cell Line; D005230:Fatty Acids, Nonesterified / Q000009:adverse effects*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D009994:Osmolar Concentration; D019308:Palmitic Acid / Q000009:adverse effects*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D005230:Fatty Acids, Nonesterified; C554846:MIRN194 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D011994:Recombinant Proteins; C495345:TLR4 protein, human; D048029:TNF Receptor-Associated Factor 6; C439524:TNF protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D019308:Palmitic Acid
keywords: TLR4; TRAF6; miR-194; palmitic acid