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Oncostatin M induces RIG-I and MDA5 expression and enhances the double-stranded RNA response in fibroblasts

Sabine Hergovits1, Christine Mais1, Claude Haan2

  • 1Medical Clinic and Policlinic II, Division of Hepatology, University Hospital Würzburg, Würzburg, Germany.

Journal of Cellular and Molecular Medicine
|June 1, 2017
PubMed

Insights

Oncostatin M (OSM) induces antiviral genes RIG-I-like receptors (RLR) in fibroblasts via STAT1 signaling. This pathway enhances cellular antiviral defense and cooperates with interferons, suggesting a role in virus protection.

Area of Science:

  • Immunology
  • Virology
  • Cellular Biology

Background:

  • Interleukin-6 (IL)-6-type cytokines modulate immune responses but lack direct antiviral activity.
  • Oncostatin M (OSM), an IL-6 family member, induces interferon-stimulated genes (ISGs), primarily involved in antigen presentation.
  • The induction of retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) by OSM has not been previously investigated.

Purpose of the Study:

  • To investigate the capability of Oncostatin M (OSM) to induce retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) in primary fibroblasts.
  • To elucidate the signaling pathways and regulatory mechanisms involved in OSM-mediated RLR induction.
  • To assess the functional implications of OSM-induced RLR expression in cellular antiviral defense.

Main Methods:

  • Primary human fibroblasts were treated with OSM to assess gene expression.
  • Western blotting and gene knockdown techniques were used to analyze signaling pathways, including STAT1, STAT3, and SOCS3.
  • Synergistic effects of OSM with interferon-gamma (IFN-γ) on RLR transcription were evaluated.
  • The impact of OSM pre-treatment on type I interferon production upon double-stranded RNA stimulation was assessed.

Main Results:

  • OSM induced the expression of RIG-I-like receptors (RLRs), including RIG-I and MDA5, and transcription factors IRF1, IRF7, and IRF9 in primary fibroblasts.
  • The induction of these genes was dependent on both tyrosine and serine phosphorylation of STAT1.
  • STAT3-dependent SOCS3 induction counter-regulated OSM-induced STAT1 phosphorylation, with STAT3 and SOCS3 knockdown enhancing RLR and IRF expression.
  • OSM and IFN-γ synergistically mediated RLR transcription, and OSM pre-treatment enhanced type I interferon production in response to double-stranded RNA.

Conclusions:

  • OSM induces RLR expression in fibroblasts through JAK/STAT1 signaling, contributing to cellular antiviral defense.
  • STAT3-dependent SOCS3 acts as a key negative regulator of this OSM-induced pathway.
  • OSM-induced signaling cooperates with interferons to enhance RLR expression, suggesting a role in non-professional immune cells' virus protection.
Keywords:
DExD/H-Box RNA helicaseRIG-ISTAT1innate immunityoncostatin M

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