title: Inhibition of IFN-γ-Induced Nitric Oxide Dependent Antimycobacterial Activity by miR-155 and C/EBPβ.
abstract: miR-155 (microRNA-155) is an important non-coding RNA in regulating host crucial biological regulators. However, its regulatory function in mycobacterium infection remains unclear. Our study demonstrates that miR-155 expression is significantly increased in macrophages after Mycobacterium marinum (M.m) infection. Transfection with anti-miR-155 enhances nitric oxide (NO) synthesis and decreases the mycobacterium burden, and vice versa, in interferon γ (IFN-γ) activated macrophages. More importantly, miR-155 can directly bind to the 3'UTR of CCAAT/enhancer binding protein β (C/EBPβ), a positive transcriptional regulator of nitric oxide synthase (NOS2), and regulate C/EBPβ expression negatively. Knockdown of C/EBPβ inhibit the production of nitric oxide synthase and promoted mycobacterium survival. Collectively, these data suggest that M.m-induced upregulation of miR-155 downregulated the expression of C/EBPβ, thus decreasing the production of NO and promoting mycobacterium survival, which may provide an insight into the function of miRNA in subverting the host innate immune response by using mycobacterium for its own profit. Understanding how miRNAs partly regulate microbicidal mechanisms may represent an attractive way to control tuberculosis infectious.
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. yw_qin@foxmail.com.|Department of Pathogen and Immunology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, China. yw_qin@foxmail.com.
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. wangqinglan2006200@163.com.
authors.forename: Qinglan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu, China. youlangzhou@163.com.
authors.forename: Youlang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pathogen and Immunology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, China. ynduan@gmail.com.
authors.forename: Yinong
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. qgao99@yahoo.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D009161:Mycobacterium / Q000276:immunology*; D009164:Mycobacterium Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D009569:Nitric Oxide / Q000276:immunology*; D000067996:RAW 264.7 Cells
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D009569:Nitric Oxide; D007371:Interferon-gamma
keywords: C/EBPβ; IFN-γ; antibacteria; microRNA-155; mycobacterium