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 tested in vitro using 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)-10 in 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 of CXCL-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 impact in vitro, although the direct antiviral effect is modest. It may have a potential impact on hepatocyte function, especially chemokine expression and antigen presentation.
Highlights
Interleukin (IL)-27 is a member of the IL-6/IL-12 family of cytokines that includes IL-12 and IL-23
We have demonstrated that there is no significant reduction in viral infectivity at 10 days post treatment with IL-27 at 100ng/ml, as observed by an immuno-fluorescence assay (IFA) of infected hepatocytes (Figure 1A)
At day 7 post-infection, HepaRG cells infected with hepatitis B virus (HBV) showed modest reductions in HBsAg levels after treatment with IL-27 (Figure 1D)
Summary
Interleukin (IL)-27 is a member of the IL-6/IL-12 family of cytokines that includes IL-12 and IL-23. 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. Conclusion: Our data indicate that IL-27 can have a significant pro-inflammatory impact in vitro, the direct antiviral effect is modest It may have a potential impact on hepatocyte function, especially chemokine expression and antigen presentation
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