Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of the Hepatitis C Virus
HCV genotype 2a strain JFH-1 replicates and produces viral particles efficiently in human hepatocellular carcinoma (huh) 7.5 cells, which provide a stable in vitro cell infection system for the hepatitis C virus (HCVcc system). Natural killer (NK) cells are large lymphoid cells that recognize and ki...
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doaj-4f6f673fff764129a13a14681a5150882020-11-25T01:59:16ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-09-01199277110.3390/ijms19092771ijms19092771Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of the Hepatitis C VirusYoo Jin Cho0Hwan Hee Lee1Hyojeung Kang2Hyosun Cho3Department of Pharmacy, College of Pharmacy, Duksung Women’s University, Seoul 132-714, KoreaDepartment of Pharmacy, College of Pharmacy, Duksung Women’s University, Seoul 132-714, KoreaCollege of Pharmacy, Research Institute of Pharmaceutical Sciences and Institute for Microorganisms, Kyungpook National University, Daegu 702-701, KoreaDepartment of Pharmacy, College of Pharmacy, Duksung Women’s University, Seoul 132-714, KoreaHCV genotype 2a strain JFH-1 replicates and produces viral particles efficiently in human hepatocellular carcinoma (huh) 7.5 cells, which provide a stable in vitro cell infection system for the hepatitis C virus (HCVcc system). Natural killer (NK) cells are large lymphoid cells that recognize and kill virus-infected cells. In this study, we investigated the interaction between NK cells and the HCVcc system. IL-10 is a typical immune regulatory cytokine that is produced mostly by NK cells and macrophages. IL-21 is one of the main cytokines that stimulate the activation of NK cells. First, we used anti-IL-10 to neutralize IL-10 in a coculture of NK cells and HCVcc. Anti-IL-10 treatment increased the maturation of NK cells by enhancing the frequency of the CD56+dim population in NK-92 cells. However, with anti-IL-10 treatment of NK cells in coculture with J6/JFH-1-huh 7.5 cells, there was a significant decrease in the expression of STAT1 and STAT5 proteins in NK-92 cells and an increase in the HCV Core and NS3 proteins. In addition, rIL-21 treatment increased the frequency of the CD56+dim population in NK-92 cells, Also, there was a dramatic increase in the expression of STAT1 and STAT5 proteins in rIL-21 pre-stimulated NK cells and a decrease in the expression of HCV Core protein in coculture with J6/JFH-1-huh 7.5 cells. In summary, we found that the functional activation of NK cells can be modulated by anti-IL-10 or rIL-21, which controls the expression of HCV proteins as well as HCV RNA replication.http://www.mdpi.com/1422-0067/19/9/2771HCVhuh 7.5natural killer cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yoo Jin Cho Hwan Hee Lee Hyojeung Kang Hyosun Cho |
spellingShingle |
Yoo Jin Cho Hwan Hee Lee Hyojeung Kang Hyosun Cho Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of the Hepatitis C Virus International Journal of Molecular Sciences HCV huh 7.5 natural killer cells |
author_facet |
Yoo Jin Cho Hwan Hee Lee Hyojeung Kang Hyosun Cho |
author_sort |
Yoo Jin Cho |
title |
Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of the Hepatitis C Virus |
title_short |
Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of the Hepatitis C Virus |
title_full |
Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of the Hepatitis C Virus |
title_fullStr |
Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of the Hepatitis C Virus |
title_full_unstemmed |
Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of the Hepatitis C Virus |
title_sort |
cytokine-modulated natural killer cells differentially regulate the activity of the hepatitis c virus |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2018-09-01 |
description |
HCV genotype 2a strain JFH-1 replicates and produces viral particles efficiently in human hepatocellular carcinoma (huh) 7.5 cells, which provide a stable in vitro cell infection system for the hepatitis C virus (HCVcc system). Natural killer (NK) cells are large lymphoid cells that recognize and kill virus-infected cells. In this study, we investigated the interaction between NK cells and the HCVcc system. IL-10 is a typical immune regulatory cytokine that is produced mostly by NK cells and macrophages. IL-21 is one of the main cytokines that stimulate the activation of NK cells. First, we used anti-IL-10 to neutralize IL-10 in a coculture of NK cells and HCVcc. Anti-IL-10 treatment increased the maturation of NK cells by enhancing the frequency of the CD56+dim population in NK-92 cells. However, with anti-IL-10 treatment of NK cells in coculture with J6/JFH-1-huh 7.5 cells, there was a significant decrease in the expression of STAT1 and STAT5 proteins in NK-92 cells and an increase in the HCV Core and NS3 proteins. In addition, rIL-21 treatment increased the frequency of the CD56+dim population in NK-92 cells, Also, there was a dramatic increase in the expression of STAT1 and STAT5 proteins in rIL-21 pre-stimulated NK cells and a decrease in the expression of HCV Core protein in coculture with J6/JFH-1-huh 7.5 cells. In summary, we found that the functional activation of NK cells can be modulated by anti-IL-10 or rIL-21, which controls the expression of HCV proteins as well as HCV RNA replication. |
topic |
HCV huh 7.5 natural killer cells |
url |
http://www.mdpi.com/1422-0067/19/9/2771 |
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