Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2016; 22(17): 4354-4361
Published online May 7, 2016. doi: 10.3748/wjg.v22.i17.4354
Inhibitory effect of miR-125b on hepatitis C virus core protein-induced TLR2/MyD88 signaling in THP-1 cells
Cheng Peng, Hua Wang, Wen-Jing Zhang, Sheng-Hua Jie, Qiao-Xia Tong, Meng-Ji Lu, Dong-Liang Yang
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
Meng-Ji Lu, Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, 45122 Essen, Germany
Author contributions: Peng C and Yang DL designed the research; Lu MJ instructed on the whole study; Peng C, Wang H and Zhang WJ performed the research; Tong QX contributed new reagents or analytic tools; Peng C and Jie SH analyzed the data; Peng C, Lu MJ and Yang DL wrote the paper.
Supported by National Natural Science Foundation of China, No. 81202321 and No. 81461130019; Transregio-SFB (TRR) of the Deutsche Forschungsgemeinschaft (DFG), No. TRR60.
Institutional review board statement: This study was approved by the Institutional Review Board of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
Conflict-of-interest statement: We declare that we have no financial or personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and company. The authors declare that there is no conflict of interests regarding the publication of this paper.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at dlyang@hust.edu.cn. Participants gave informed consent for data sharing. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dong-Liang Yang, MD, PhD, DSc. (Med), Professor, Chief, Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, Hubei Province, China. dlyang@hust.edu.cn
Telephone: +86-27-85726978 Fax: +86-27-85726398
Received: December 20, 2015
Peer-review started: December 31, 2015
First decision: January 28, 2016
Revised: February 22, 2016
Accepted: March 14, 2016
Article in press: March 14, 2016
Published online: May 7, 2016
Processing time: 121 Days and 7.9 Hours
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.

Keywords: miR-125b; Hepatitis virus C; Toll like receptor 2; Monocytes; Innate immunity

Core tip: Increasingly many studies have shown that microRNAs are critical regulators of the innate immune response. Many anti-pathogen pathways, including the pattern recognition Toll-like receptor (TLR)-mediated signaling pathway, are known to be regulated by a network of microRNAs. Here we investigated the possible role of miR-125b in regulating the monocyte immune responses induced by HCV core protein through TLR2/MyD88 signaling. Our findings indicated that miR-125b may function as a negative regulator of HCV-induced cellular events, which may provide insight into the role of miR-125b in the innate immune responses of monocytes to HCV.