Interleukin-27 displays interferon-gamma-like functions in human hepatoma cells and hepatocytes

Hepatology. 2009 Aug;50(2):585-91. doi: 10.1002/hep.22988.

Abstract

Interleukin-27 (IL-27) is a cytokine belonging to the IL-6/IL-12 cytokine family. It is secreted by antigen-presenting cells, strongly acts on T cells, and also stimulates innate immune cells. In most studies, the effects of IL-27 on T cells were investigated; however, not much is known about possible effects of IL-27 on other cell types. IL-27 signals via the common IL-6-type cytokine receptor chain gp130 and the IL-27-specific chain WSX-1. Given the importance of gp130 in regulating liver responses such as the acute phase response or liver regeneration, we investigated whether IL-27 could also have a function in liver cells. We find that IL-27 stimulates hepatoma cells and hepatocytes by inducing a sustained signal transducer and activator of transcription (STAT)1 and STAT3 activation. Whereas the STAT3 mediated responses to IL-27 (gamma-fibrinogen and hepcidin induction) are not detectable, we observe an interferon-gamma (IFN-gamma)-like STAT1 response leading to the induction of interferon-regulated proteins such as STAT1, STAT2, interferon response factor (IRF)-1, IRF-9, myxovirus resistance A and guanylate binding protein 2.

Conclusion: Our study provides evidence for a function of IL-27 in hepatoma cells and hepatocytes and shows that IL-27 responses are not restricted to the classical immune cells. Our results suggest that IL-27 exerts IFN-like functions in liver cells and that it can contribute to the antiviral response in these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / metabolism
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Fibrinogen / metabolism
  • Gene Expression Regulation
  • Hepatocytes / metabolism*
  • Hepcidins
  • Humans
  • Interferon-gamma / metabolism
  • Interleukins / immunology
  • Interleukins / metabolism*
  • Liver Neoplasms / metabolism*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • STAT1 Transcription Factor / metabolism*
  • STAT3 Transcription Factor / metabolism
  • Virus Replication

Substances

  • Antimicrobial Cationic Peptides
  • HAMP protein, human
  • Hamp protein, rat
  • Hepcidins
  • Interleukins
  • MYDGF protein, human
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Interferon-gamma
  • Fibrinogen