Hepatocyte growth factor in dampening liver immune-mediated pathology in acute viral hepatitis without compromising antiviral activity

Renan Aguilar-Valenzuela, Eric D. Carlsen, Yuejin Liang, Lynn Soong, Jiaren Sun

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background and Aim: Hepatocyte growth factor (HGF) is a pleiotropic cytokine related with cell proliferation and survival; however, its role in viral hepatitis is not elucidated. In this study, we studied HGF immune role in viral hepatitis. Methods: Mice received hydrodynamically delivered HGF plasmid or control plasmid and then infected with adenovirus, and parameters of immune-mediated liver damage were evaluated. We studied dendritic cell (DC) activation in the presence of HGF. T cells collected from infected mice were restimulated with virally infected DC to measure cytokine production in vitro. Results: HGF ameliorated the liver inflammation during viral hepatitis as alanine transferase, intrahepatic lymphocytes, and splenocyte counts were diminished by HGF. Lower histological scores of liver pathology were observed in the HGF group. DC from the HGF group expressed reduced CD40. The hepatic expression and serum concentration of IL-12p40 were diminished in HGF-transfected mice. In vitro experiments with DC confirmed that HGF diminished CD40 expression and IL-12p40 production. The expression and serum levels of IFN-γ, IL-6 and CXCL9 were significantly decreased in the HGF group. HGF overexpression diminished the expression and concentration of IL-10 and TGF-β. The frequency of PD-1+Tim-3+ in CD8 T cells was decreased by HGF overexpression. Moreover, T cells in the HGF group at day 14 secreted more IFN-γ and TNF-α than those in the control group when restimulated with virally infected DC. Conclusion: HGF modulated DC activation and T cell priming, thereby limiting the immune-mediated damage in the liver. However, viral clearance was not compromised by HGF.

Original languageEnglish (US)
Pages (from-to)878-886
Number of pages9
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume29
Issue number4
DOIs
StatePublished - 2014

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Hepatocyte Growth Factor
Hepatitis
Antiviral Agents
Pathology
Liver
Dendritic Cells
Interleukin-12 Subunit p40
T-Lymphocytes
Plasmids
Cytokines
Lymphocyte Count
Transferases
Serum
Adenoviridae
Alanine
Interleukin-10

Keywords

  • Dendritic cells
  • Hepatocyte growth factor
  • T cell inhibition
  • Viral hepatitis

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

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title = "Hepatocyte growth factor in dampening liver immune-mediated pathology in acute viral hepatitis without compromising antiviral activity",
abstract = "Background and Aim: Hepatocyte growth factor (HGF) is a pleiotropic cytokine related with cell proliferation and survival; however, its role in viral hepatitis is not elucidated. In this study, we studied HGF immune role in viral hepatitis. Methods: Mice received hydrodynamically delivered HGF plasmid or control plasmid and then infected with adenovirus, and parameters of immune-mediated liver damage were evaluated. We studied dendritic cell (DC) activation in the presence of HGF. T cells collected from infected mice were restimulated with virally infected DC to measure cytokine production in vitro. Results: HGF ameliorated the liver inflammation during viral hepatitis as alanine transferase, intrahepatic lymphocytes, and splenocyte counts were diminished by HGF. Lower histological scores of liver pathology were observed in the HGF group. DC from the HGF group expressed reduced CD40. The hepatic expression and serum concentration of IL-12p40 were diminished in HGF-transfected mice. In vitro experiments with DC confirmed that HGF diminished CD40 expression and IL-12p40 production. The expression and serum levels of IFN-γ, IL-6 and CXCL9 were significantly decreased in the HGF group. HGF overexpression diminished the expression and concentration of IL-10 and TGF-β. The frequency of PD-1+Tim-3+ in CD8 T cells was decreased by HGF overexpression. Moreover, T cells in the HGF group at day 14 secreted more IFN-γ and TNF-α than those in the control group when restimulated with virally infected DC. Conclusion: HGF modulated DC activation and T cell priming, thereby limiting the immune-mediated damage in the liver. However, viral clearance was not compromised by HGF.",
keywords = "Dendritic cells, Hepatocyte growth factor, T cell inhibition, Viral hepatitis",
author = "Renan Aguilar-Valenzuela and Carlsen, {Eric D.} and Yuejin Liang and Lynn Soong and Jiaren Sun",
year = "2014",
doi = "10.1111/jgh.12456",
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volume = "29",
pages = "878--886",
journal = "Journal of Gastroenterology and Hepatology (Australia)",
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TY - JOUR

T1 - Hepatocyte growth factor in dampening liver immune-mediated pathology in acute viral hepatitis without compromising antiviral activity

AU - Aguilar-Valenzuela, Renan

AU - Carlsen, Eric D.

AU - Liang, Yuejin

AU - Soong, Lynn

AU - Sun, Jiaren

PY - 2014

Y1 - 2014

N2 - Background and Aim: Hepatocyte growth factor (HGF) is a pleiotropic cytokine related with cell proliferation and survival; however, its role in viral hepatitis is not elucidated. In this study, we studied HGF immune role in viral hepatitis. Methods: Mice received hydrodynamically delivered HGF plasmid or control plasmid and then infected with adenovirus, and parameters of immune-mediated liver damage were evaluated. We studied dendritic cell (DC) activation in the presence of HGF. T cells collected from infected mice were restimulated with virally infected DC to measure cytokine production in vitro. Results: HGF ameliorated the liver inflammation during viral hepatitis as alanine transferase, intrahepatic lymphocytes, and splenocyte counts were diminished by HGF. Lower histological scores of liver pathology were observed in the HGF group. DC from the HGF group expressed reduced CD40. The hepatic expression and serum concentration of IL-12p40 were diminished in HGF-transfected mice. In vitro experiments with DC confirmed that HGF diminished CD40 expression and IL-12p40 production. The expression and serum levels of IFN-γ, IL-6 and CXCL9 were significantly decreased in the HGF group. HGF overexpression diminished the expression and concentration of IL-10 and TGF-β. The frequency of PD-1+Tim-3+ in CD8 T cells was decreased by HGF overexpression. Moreover, T cells in the HGF group at day 14 secreted more IFN-γ and TNF-α than those in the control group when restimulated with virally infected DC. Conclusion: HGF modulated DC activation and T cell priming, thereby limiting the immune-mediated damage in the liver. However, viral clearance was not compromised by HGF.

AB - Background and Aim: Hepatocyte growth factor (HGF) is a pleiotropic cytokine related with cell proliferation and survival; however, its role in viral hepatitis is not elucidated. In this study, we studied HGF immune role in viral hepatitis. Methods: Mice received hydrodynamically delivered HGF plasmid or control plasmid and then infected with adenovirus, and parameters of immune-mediated liver damage were evaluated. We studied dendritic cell (DC) activation in the presence of HGF. T cells collected from infected mice were restimulated with virally infected DC to measure cytokine production in vitro. Results: HGF ameliorated the liver inflammation during viral hepatitis as alanine transferase, intrahepatic lymphocytes, and splenocyte counts were diminished by HGF. Lower histological scores of liver pathology were observed in the HGF group. DC from the HGF group expressed reduced CD40. The hepatic expression and serum concentration of IL-12p40 were diminished in HGF-transfected mice. In vitro experiments with DC confirmed that HGF diminished CD40 expression and IL-12p40 production. The expression and serum levels of IFN-γ, IL-6 and CXCL9 were significantly decreased in the HGF group. HGF overexpression diminished the expression and concentration of IL-10 and TGF-β. The frequency of PD-1+Tim-3+ in CD8 T cells was decreased by HGF overexpression. Moreover, T cells in the HGF group at day 14 secreted more IFN-γ and TNF-α than those in the control group when restimulated with virally infected DC. Conclusion: HGF modulated DC activation and T cell priming, thereby limiting the immune-mediated damage in the liver. However, viral clearance was not compromised by HGF.

KW - Dendritic cells

KW - Hepatocyte growth factor

KW - T cell inhibition

KW - Viral hepatitis

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JO - Journal of Gastroenterology and Hepatology (Australia)

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