title: Impact of IL-27 on hepatocyte antiviral gene expression and function.
abstract: Background:Interleukin (IL)-27 is a member of the IL-6/IL-12 family of cytokines. It is a potent cytokine, with potential antiviral impact, and has been shown to play a role in modulating functions of diverse cell types, including Th1, Th2, and NK and B cells, demonstrating both pro- and anti-inflammatory roles.  In hepatocytes, it is capable of inducing signal transducer and activator of transcription (STAT)1, STAT3 and interferon-stimulated genes.Methods:To address its role in viral hepatitis, the antiviral activity of IL-27 against hepatitis C virus (HCV) and hepatitis B virus (HBV) was testedin vitrousing cell-culture-derived infectious HCV (HCVcc) cell culture system and the HepaRG HBV cell culture model. To further investigate the impact of IL-27 on hepatocytes, Huh7.5 cells were treated with IL-27 to analyse the differentially expressed genes by microarray analysis. Furthermore, by quantitative PCR, we analyzed the up-regulation of chemokine(CXCL)-10in response to IL-27.Results:In both HCV and HBV infection models, we observed only a modest direct antiviral effect. Microarray analysis showed that the up-regulated genes mostly belonged to antigen presentation and DNA replication pathways, and involved strong up-regulation ofCXCL-10, a gene associated with liver inflammation. Overall, gene set enrichment analysis showed a striking correlation of these genes with those up-regulated in response to related cytokines in diverse cell populations.Conclusion:Our data indicate that IL-27 can have a significant pro-inflammatory impactin vitro, although the direct antiviral effect is modest. It may have a potential impact on hepatocyte function, especially chemokine expression and antigen presentation.
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: Narayan
authors.initials: N
authors.lastname: Ramamurthy
authors.affiliation: Sacrocuore Hospital, University of Padua, Padua, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Boninsegna
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Adams
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Natasha
authors.initials: N
authors.lastname: Sahgal
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Lockstone
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Dilair
authors.initials: D
authors.lastname: Baban
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Marchi
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: Paul
authors.identifier: 0000-0003-4307-9161
authors.initials: P
authors.lastname: Klenerman
keywords: CXCL10; Hepatitis C virus; IL-27; cytokines; gene array; hepatitis B virus; hepatocytes; inflammation