Inhibitory effect of miR-125b on hepatitis C virus core protein-induced TLR2/My D88 signaling in THP-1 cells |
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Authors: | Cheng Peng Hua Wang Wen-Jing Zhang Sheng-Hua Jie Qiao-Xia Tong Meng-Ji Lu Dong-Liang Yang |
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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, ChinaMeng-Ji Lu, Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, 45122 Essen, Germany |
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Abstract: | AIM: 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.CONCLUSION: 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. |
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Keywords: | miR-125b Hepatitis virus C Toll like receptor 2 Monocytes Innate immunity |
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