Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2017; 23(32): 5895-5903
Published online Aug 28, 2017. doi: 10.3748/wjg.v23.i32.5895
(-)-Epigallocatechin-3-gallate enhances poly I:C-induced interferon-λ1 production and inhibits hepatitis C virus replication in hepatocytes
Yi-Zhong Wang, Jie-Liang Li, Xu Wang, Ting Zhang, Wen-Zhe Ho
Yi-Zhong Wang, Ting Zhang, Department of Infectious Diseases, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200040, China
Jie-Liang Li, Xu Wang, Wen-Zhe Ho, Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, United States
Author contributions: Wang YZ, Zhang T and Ho WZ designed the research; Wang YZ and Li JL performed the research; Wang X contributed new reagents/analytical tools; Wang YZ and Zhang T analyzed the data; Wang YZ and Zhang T wrote the paper.
Supported by the National Natural Science Foundation of China, No. 81500449; the Natural Science Foundation of Shanghai, No. 14ZR1434200; Shanghai Municipal Commission of Health and Family Planning, No. 20144Y0175; the Scientific Research Foundation for the Returned Overseas Chinese Scholars; and the State Education Ministry of China, No. 20150909-6.
Conflict-of-interest statement: The authors declare no conflict of interest associated with this manuscript.
Data sharing statement: 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: Ting Zhang, MD, PhD, Department of Infectious Diseases, Shanghai Children’s Hospital, Shanghai Jiao Tong University, 355 Luding Road, Shanghai 200040, China. zhangt@shchildren.com.cn
Telephone: +86-21-52976338 Fax: +86-21-52976338
Received: January 4, 2017
Peer-review started: January 6, 2017
First decision: March 16, 2017
Revised: March 30, 2017
Accepted: July 22, 2017
Article in press: July 24, 2017
Published online: August 28, 2017
Abstract
AIM

To investigate the effect of (-)-epigallocatechin-3-gallate (EGCG) on polyinosinic-polycytidylic acid (poly I:C)-triggered intracellular innate immunity against hepatitis C virus (HCV) in hepatocytes.

METHODS

A cell culture model of HCV infection was generated by infecting a hepatoma cell line, Huh7, with HCV JFH-1 strain (JFH-1-Huh7). Poly I:C with a high molecular weight and EGCG were used to stimulate the JFH-1-Huh7 cells. Real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of intracellular mRNAs and of intracellular and extracellular HCV RNA. Enzyme-linked immunosorbent assay was used to evaluate the interferon (IFN)-λ1 protein level in the cell culture supernatant. Immunostaining was used to examine HCV core protein expression in Huh7 cells.

RESULTS

Our recent study showed that HCV replication could impair poly I:C-triggered intracellular innate immune responses in hepatocytes. In the current study, we showed that EGCG treatment significantly increased the poly I:C-induced expression of Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I, and IFN-λ1 in JFH-1-Huh7 cells. In addition, supplementation with EGCG increased the poly I:C-mediated antiviral activity in JFH-1-Huh7 cells at the intracellular and extracellular HCV RNA and protein levels. Further investigation of the mechanisms showed that EGCG treatment significantly enhanced the poly I:C-induced expression of IFN-regulatory factor 9 and several antiviral IFN-stimulated genes, including ISG15, ISG56, myxovirus resistance A, and 2’-5’-oligoadenylate synthetase 1, which encode the key antiviral elements in the IFN signaling pathway.

CONCLUSION

Our observations provide experimental evidence that EGCG has the ability to enhance poly I:C-induced intracellular antiviral innate immunity against HCV replication in hepatocytes.

Keywords: (-)-Epigallocatechin-3-gallate, Toll-like receptor 3, Retinoic acid-inducible gene I, IFN-λ1, Hepatitis C virus, IFN-stimulated genes

Core tip: The interactions between hepatitis C virus (HCV) and the host immune system in the liver play a key role in the immunopathogenesis of HCV-induced diseases. We showed here that (-)-epigallocatechin-3-gallate (EGCG) treatment could significantly increase the poly I:C-induced expression of TLR3, RIG-I and interferon (IFN)-λ1 in JFH-1-Huh7 cells. In addition, supplementation with EGCG enhanced poly I:C-mediated viral inhibition in JFH-1-Huh7 cells at both RNA and protein levels. Further investigation of the mechanisms showed that EGCG treatment significantly enhanced the poly I:C-induced expression of IFN-regulatory factor 9 and several IFN-stimulated genes. It would be interesting to investigate the possible use of EGCG in combination with current antiviral drugs for HCV therapy.