Interleukin 29 enhances expression of toll receptor 3 and mediates antiviral signals in human keratinocytes

Objective Interleukin 29 (IL-29) is a class II cytokine and displays numerous immune functions other than its antiviral and antiproliferation activities. This study is focused on the effect of IL-29 on human keratinocytes (KCs). Methods Primary KCs were stimulated by various concentrations of IL-29 for different time periods, and antiviral proteins and TLR3 gene expression were then analyzed by real-time PCR. The signal pathways activated by IL-29 in KCs were detected by western blot. The antiviral activity of IL-29 was determined by methylthiazolyldiphenyl-tetrazolium bromide, and small interfering RNA knockdown was used to analyze the role of toll receptor 3 (TLR3) in the antiviral activity of IL-29. Results IL-29 was able to induce expression of antiviral proteins and TLR3 gene expression in KCs. IL-29 pretreatment strongly enhanced herpes simplex virus type 1 (HSV-1)-induced expression of the interferon beta (IFN-beta) gene and protected the KCs from HSV-1 challenge. The IL-29 antiviral activity was partially dependent on TLR3 expression induced by this cytokine, and mechanistic studies demonstrated that the regulation of TLR3 expression by IL-29 might be partially dependent on Janus kinase/signal transducer and activator of transcription (JAK-STATs) activation. Conclusion IL-29-induced TLR3 expression is involved in antiviral activity of IL-29 in KCs, which suggests a feasible method to cure certain viral infections of the skin.