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HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes
BACKGROUND: Macrophages play critical roles in innate immune response in the liver. Whether macrophages participate in liver innate immunity against HCV replication is poorly understood OBJECTIVES: The aim of this study was to investigate the role of macrophages in liver innate immunity against HCV...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Kowsar
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546812/ https://www.ncbi.nlm.nih.gov/pubmed/26322111 http://dx.doi.org/10.5812/hepatmon.29282 |
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author | Wang, Yizhong Li, Jieliang Wang, Xu Zhou, Yu Zhang, Ting Ho, Wenzhe |
author_facet | Wang, Yizhong Li, Jieliang Wang, Xu Zhou, Yu Zhang, Ting Ho, Wenzhe |
author_sort | Wang, Yizhong |
collection | PubMed |
description | BACKGROUND: Macrophages play critical roles in innate immune response in the liver. Whether macrophages participate in liver innate immunity against HCV replication is poorly understood OBJECTIVES: The aim of this study was to investigate the role of macrophages in liver innate immunity against HCV replication. MATERIALS AND METHODS: Freshly isolated monocytes were purified from peripheral blood of healthy adult donors. Macrophages refer to 7-day-cultured monocytes in vitro. A hepatoma cell line (Huh7) was infected with HCV JFH-1 to generate in vitro HCV infectious system. RT-PCR was used to determine HCV RNA and mRNA levels of genes expression. ELISA was used to measure the protein level of interferon-α (IFN-α) and western blot was used to determine protein expression level of Toll-like receptor 3 (TLR3). RESULTS: HCV dsRNA induced the expression of type I IFN (IFN-α/β) in monocyte-derived macrophages. HCV dsRNA also induced the expression of TLR3 and IFN regulatory factor-7 (IRF-7), the key regulators of the IFN signaling pathway. When HCV JFH-1-infected Huh7 cells were co-cultured with macrophages activated with HCV dsRNA or incubated in media conditioned with supernatant (SN) from HCV dsRNA-activated macrophages, HCV replication was significantly suppressed. This macrophage SN action on HCV inhibition was mediated through type I IFN, which was evidenced by the observation that antibody to type I IFN receptor could neutralize the macrophages-mediated anti-HCV effect. The role of type I IFN in macrophages-mediated anti-HCV activity is further supported by the observation that HCV dsRNA-activated macrophages SN treatment induced the expression of several IFN-stimulated genes (ISGs), ISG15, ISG56, OAS-1, OAS-2, MxA and Viperin in HCV-infected Huh7 cells. CONCLUSIONS: Macrophages may play an important role in liver innate immunity against HCV replication through a type I IFN-dependent mechanism. |
format | Online Article Text |
id | pubmed-4546812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Kowsar |
record_format | MEDLINE/PubMed |
spelling | pubmed-45468122015-08-30 HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes Wang, Yizhong Li, Jieliang Wang, Xu Zhou, Yu Zhang, Ting Ho, Wenzhe Hepat Mon Research Article BACKGROUND: Macrophages play critical roles in innate immune response in the liver. Whether macrophages participate in liver innate immunity against HCV replication is poorly understood OBJECTIVES: The aim of this study was to investigate the role of macrophages in liver innate immunity against HCV replication. MATERIALS AND METHODS: Freshly isolated monocytes were purified from peripheral blood of healthy adult donors. Macrophages refer to 7-day-cultured monocytes in vitro. A hepatoma cell line (Huh7) was infected with HCV JFH-1 to generate in vitro HCV infectious system. RT-PCR was used to determine HCV RNA and mRNA levels of genes expression. ELISA was used to measure the protein level of interferon-α (IFN-α) and western blot was used to determine protein expression level of Toll-like receptor 3 (TLR3). RESULTS: HCV dsRNA induced the expression of type I IFN (IFN-α/β) in monocyte-derived macrophages. HCV dsRNA also induced the expression of TLR3 and IFN regulatory factor-7 (IRF-7), the key regulators of the IFN signaling pathway. When HCV JFH-1-infected Huh7 cells were co-cultured with macrophages activated with HCV dsRNA or incubated in media conditioned with supernatant (SN) from HCV dsRNA-activated macrophages, HCV replication was significantly suppressed. This macrophage SN action on HCV inhibition was mediated through type I IFN, which was evidenced by the observation that antibody to type I IFN receptor could neutralize the macrophages-mediated anti-HCV effect. The role of type I IFN in macrophages-mediated anti-HCV activity is further supported by the observation that HCV dsRNA-activated macrophages SN treatment induced the expression of several IFN-stimulated genes (ISGs), ISG15, ISG56, OAS-1, OAS-2, MxA and Viperin in HCV-infected Huh7 cells. CONCLUSIONS: Macrophages may play an important role in liver innate immunity against HCV replication through a type I IFN-dependent mechanism. Kowsar 2015-08-30 /pmc/articles/PMC4546812/ /pubmed/26322111 http://dx.doi.org/10.5812/hepatmon.29282 Text en Copyright © 2015, Kowsar Corp. http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited. |
spellingShingle | Research Article Wang, Yizhong Li, Jieliang Wang, Xu Zhou, Yu Zhang, Ting Ho, Wenzhe HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes |
title | HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes |
title_full | HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes |
title_fullStr | HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes |
title_full_unstemmed | HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes |
title_short | HCV dsRNA-Activated Macrophages Inhibit HCV Replication in Hepatocytes |
title_sort | hcv dsrna-activated macrophages inhibit hcv replication in hepatocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546812/ https://www.ncbi.nlm.nih.gov/pubmed/26322111 http://dx.doi.org/10.5812/hepatmon.29282 |
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