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

Inflamm Res. 2011 Nov;60(11):1031-7. doi: 10.1007/s00011-011-0364-z. Epub 2011 Aug 17.

Abstract

Objective: Interleukin 29 (IL-29) is a class II cytokine and displays numerous immune functions other than its anti-viral 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 β (IFN-β) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / metabolism
  • Cell Line
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation*
  • Herpes Simplex / immunology
  • Herpesvirus 1, Human / metabolism
  • Humans
  • Interferon-beta / metabolism
  • Interferons
  • Interleukins / metabolism*
  • Keratinocytes / metabolism*
  • Keratinocytes / virology
  • Phosphorylation
  • RNA / metabolism
  • RNA, Small Interfering / metabolism
  • STAT Transcription Factors / metabolism
  • Signal Transduction
  • Skin / virology*
  • Toll-Like Receptor 3 / metabolism*

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interleukins
  • RNA, Small Interfering
  • STAT Transcription Factors
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • RNA
  • Interferon-beta
  • Interferons