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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología experimental > DA - CIMA - Terapia génica y Hepatología - Inmunología experimental - Artículos de revista >

Oncostatin M enhances the antiviral effects of type I interferon and activates immunostimulatory functions in liver epithelial cells
Authors: Larrea, E. (Esther)
Aldabe, R. (Rafael)
Gonzalez, I. (Iranzu)
Segura, V. (Víctor)
Sarobe, P. (Pablo)
Echeverria, I. (Itziar)
Prieto, J. (Jesús)
Keywords: Epithelial Cells/immunology
Hepacivirus/immunology
Hepatitis A virus/immunology
Interferon Type I/immunology
Liver/immunology
Oncostatin M/immunology
Issue Date: 2009
Publisher: American Society for Microbiology
Publisher version: http://jvi.asm.org/content/83/7/3298
ISSN: 1098-5514
Citation: Larrea E, Aldabe R, Gonzalez I, Segura V, Sarobe P, Echeverria I, et al. Oncostatin M enhances the antiviral effects of type I interferon and activates immunostimulatory functions in liver epithelial cells. J Virol 2009 Apr;83(7):3298-3311.
Abstract
Oncostatin M (OSM) is released together with type I interferon (IFN) by activated dendritic cells, suggesting a concerted action of these cytokines in the biological response against infection. We found that OSM increases the antiviral effect of IFN-alpha in Huh7 hepatoma cells infected with hepatitis A or hepatitis C virus and synergizes with IFN-alpha in the induction of antiviral genes. The combination of OSM and IFN-alpha led to upregulation of both STAT1 and STAT3 together with intense and prolonged activation of STAT1, STAT3, and Jak1. OSM with or without IFN-alpha also activated p38 mitogen-activated protein kinase, which is known to enhance transcription of IFN-alpha-inducible genes. Interestingly, OSM combined with IFN-alpha strongly induced immunoproteasome genes and other genes involved in antigen processing and presentation. Moreover, OSM, alone or in combination with IFN-alpha, upregulated relevant innate immunity molecules and increased the expression of intracellular adhesion molecule 1 and interleukin-15 receptor alpha (IL-15Ralpha) in liver cells. Hepatoma cells transfected with a plasmid encoding a viral antigen were able to activate effector T cells when pretreated with IFN-alpha plus OSM but not with each cytokine separately. Also, OSM, more than IFN-alpha, augmented the ability of Huh7 cells to transpresent IL-15 to responding lymphocytes and increased the immunostimulatory activity of liver epithelial cells by presenting a short viral peptide to sensitized cytotoxic T cells. In conclusion, OSM enhances the antiviral effects of type I interferon and cooperates with it in the induction of adaptive immune responses to pathogens. These findings may have therapeutic implications.
Permanent link: http://hdl.handle.net/10171/21601
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Inmunología clínica - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología experimental - Artículos de revista

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