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.
journal_name
J Viroljournal_title
Journal of virologyauthors
Larrea E,Aldabe R,Gonzalez I,Segura V,Sarobe P,Echeverria I,Prieto Jdoi
10.1128/JVI.02167-08subject
Has Abstractpub_date
2009-04-01 00:00:00pages
3298-311issue
7eissn
0022-538Xissn
1098-5514pii
JVI.02167-08journal_volume
83pub_type
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:1991-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2012-03-01 00:00:00