title: miR-206 modulates lipopolysaccharide-mediated inflammatory cytokine production in human astrocytes.
abstract: Astrocyte-derived inflammation is a common component of acute or chronic injury in the central nervous system. MicroRNAs (miRNAs) are small non-coding RNAs that play important regulatory roles in the inflammatory response. In this study, we found that miR-206 is induced upon stimulation with lipopolysaccharide. Overexpression of miR-206 in astrocytes led to increased expression of inflammatory cytokines (interleukin-6, interleukin-1β, CCL5) upon exposure to lipopolysaccharide, whereas knockdown of miR-206 had completely opposite effects. We used a combination of bioinformatics and experimental techniques to demonstrate that NR4A2, which belongs to the nuclear receptor (NR) 4 family of orphan nuclear receptors, is a direct target of miR-206. Overexpression of miR-206 mimics decreased the activity of a luciferase reporter containing the NR4A2 3'-untranslated region and led to decreased NR4A2 mRNA and protein levels. In contrast, ectopic expression of an miR-206 inhibitor led to elevated NR4A2 expression. We also found that miR-206 modulated the lipopolysaccharide-induced proinflammatory response by targeting NR4A2 and activating nuclear factor-kappa B activity. Finally, we demonstrated that the transcription factor AP-1 plays a critical role in lipopolysaccharide-induced expression of miR-206 and that the extracellular signal-regulated kinase signaling pathway contributes to the regulation of miR-206 level in astrocytes. These data demonstrate that miR-206 positively regulates the lipopolysaccharide-induced inflammatory response in human astrocytes.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
authors.forename: Ali
authors.initials: A
authors.lastname: Zohaib
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
authors.forename: Yunchun
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
authors.forename: Bibo
authors.initials: B
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
authors.forename: Shengfeng
authors.initials: S
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Song
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China; Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China. Electronic address: sbcao@mail.hzau.edu.cn.
authors.forename: Shengbo
authors.initials: S
authors.lastname: Cao
mesh_terms: D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C546087:MIRN206 microRNA, human; D035683:MicroRNAs; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D018808:Transcription Factor AP-1; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Astrocyte; Inflammation; LPS; NR4A2; miR-206