Interleukin‐29 uses a type 1 interferon‐like program to promote antiviral responses in human hepatocytes†

作者：Sean E. Doyle, Heidi Schreckhise, Kien Khuu-Duong, Katherine Henderson, Robert Rosler, Harold Haydon Storey, Lena Yue Yao, Hong Liu, Fariba Barahmand-Pour, Pallavur V. Sivakumar, Chung Chan, Carl Birks, Don Foster, Christopher H. Clegg, Perdita Wietzke‐Braun, Sabine Mihm, Kevin M. Klucher · 发表于：Hepatology · 年份：2006 · DOI：10.1002/hep.21312 · 被引用次数：347 · 研究领域：Cytokine Signaling Pathways and Interactions、interferon and immune responses、Virus-based gene therapy research

Interleukin-28A (IL-28A), IL-28B and IL-29 are a family of class II cytokines that stimulate antiviral responses through a heterodimeric receptor that is distinct from the type I interferon (IFN) receptor. To better understand how this newly described family of cytokines regulates the antiviral state, we compared various cellular responses elicited by IL-29 and IFN-alpha. Here we show that these cytokines stimulate similar patterns of signal transducer and activator of transcription 1 (STAT-1), -2, -3, and -5 phosphorylation and nearly identical patterns of gene expression when analyzed in two distinct cell types by microarray analysis. Interestingly, the IL-29 receptor is preferentially expressed on primary hepatocytes within normal liver and pegylated forms of IL-29 and IFN-alpha induced equivalent 2'5' oligoadenylate synthetase (OAS) and MX1 gene expression in this cell type. Pegylated IL-29 also produced a significant reduction in human hepatitis B and hepatitis C viral load in vitro and reduced the cytopathic effect caused by the fully replicating flavivirus, West Nile virus. In conclusion, IL-29 and IFN-alpha stimulate identical antiviral responses despite their utilization of different receptors. This fact, combined with significant receptor expression in hepatitis virus-infected livers, suggests that IL-29 may have therapeutic value against chronic viral hepatitis in human patients.