title: Inhibitory effect of miR-125b on hepatitis C virus core protein-induced TLR2/MyD88 signaling in THP-1 cells.
abstract: OBJECTIVE
  To investigate the role of miR-125b in regulating monocyte immune responses induced by hepatitis C virus (HCV) core protein.
  
  
  METHODS
  Monocytic THP-1 cells were treated with various concentrations of recombinant HCV core protein, and cytokines and miR-125b expression in these cells were analyzed. The requirement of Toll-like receptor 2 (TLR2) or MyD88 gene for HCV core protein-induced immune responses was determined by the transfection of THP-1 cells with gene knockdown vectors expressing either TLR2 siRNA or MyD88 siRNA. The effect of miR-125b overexpression on TLR2/MyD88 signaling was examined by transfecting THP-1 cells with miR-125b mimic RNA oligos.
  
  
  RESULTS
  In response to HCV core protein stimulation, cytokine production was up-regulated and miR-125b expression was down-regulated in THP-1 cells. The modulatory effect of HCV core protein on cellular events was dose-dependent and required functional TLR2 or MyD88 gene. Forced miR-125b expression abolished the HCV core protein-induced enhancement of tumor necrosis factor-α, interleukin (IL)-6, and IL-10 expression by 66%, 54%, and 66%, respectively (P < 0.001), by inhibiting MyD88-mediated signaling, including phosphorylation of NF-κBp65, ERK, and P38.
  
  
  CONCLUSIONS
  The inverse correlation between miR-125b and cytokine expression after HCV core challenge suggests that miR-125b may negatively regulate HCV-induced immune responses by targeting TLR2/MyD88 signaling in monocytes.
authors.affiliation: Cheng Peng, Hua Wang, Wen-Jing Zhang, Sheng-Hua Jie, Qiao-Xia Tong, Dong-Liang Yang, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.affiliation: Cheng Peng, Hua Wang, Wen-Jing Zhang, Sheng-Hua Jie, Qiao-Xia Tong, Dong-Liang Yang, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Cheng Peng, Hua Wang, Wen-Jing Zhang, Sheng-Hua Jie, Qiao-Xia Tong, Dong-Liang Yang, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Cheng Peng, Hua Wang, Wen-Jing Zhang, Sheng-Hua Jie, Qiao-Xia Tong, Dong-Liang Yang, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
authors.forename: Sheng-Hua
authors.initials: SH
authors.lastname: Jie
authors.affiliation: Cheng Peng, Hua Wang, Wen-Jing Zhang, Sheng-Hua Jie, Qiao-Xia Tong, Dong-Liang Yang, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
authors.forename: Qiao-Xia
authors.initials: QX
authors.lastname: Tong
authors.affiliation: Cheng Peng, Hua Wang, Wen-Jing Zhang, Sheng-Hua Jie, Qiao-Xia Tong, Dong-Liang Yang, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
authors.forename: Meng-Ji
authors.initials: MJ
authors.lastname: Lu
authors.affiliation: Cheng Peng, Hua Wang, Wen-Jing Zhang, Sheng-Hua Jie, Qiao-Xia Tong, Dong-Liang Yang, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Yang
mesh_terms: D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D035683:MicroRNAs / Q000502:physiology*; D009000:Monocytes / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014758:Viral Core Proteins / Q000502:physiology*
chemical_list: C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; C531888:MIRN125 microRNA, human; C507779:MYD88 protein, human; D035683:MicroRNAs; D053594:Myeloid Differentiation Factor 88; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; D016753:Interleukin-10
keywords: Hepatitis virus C; Innate immunity; Monocytes; Toll like receptor 2; miR-125b