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Hergovits, Sabine; Mais, Christine; Haan, Claude; Costa‐Pereira, Ana P.; Hermanns, Heike M.

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

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  • Medientyp: E-Artikel
  • Titel: Oncostatin M induces RIG‐I and MDA5 expression and enhances the double‐stranded RNA response in fibroblasts
  • Beteiligte: Hergovits, Sabine; Mais, Christine; Haan, Claude; Costa‐Pereira, Ana P.; Hermanns, Heike M.
  • Erschienen: Wiley, 2017
  • Erschienen in: Journal of Cellular and Molecular Medicine, 21 (2017) 11, Seite 3087-3099
  • Sprache: Englisch
  • DOI: 10.1111/jcmm.13221
  • ISSN: 1582-4934; 1582-1838
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Interleukin (<jats:styled-content style="fixed-case">IL</jats:styled-content>)‐6‐type cytokines have no direct antiviral activity; nevertheless, they display immune‐modulatory functions. Oncostatin M (<jats:styled-content style="fixed-case">OSM</jats:styled-content>), a member of the <jats:styled-content style="fixed-case">IL</jats:styled-content>‐6 family, has recently been shown to induce a distinct number of classical interferon stimulated genes (<jats:styled-content style="fixed-case">ISG</jats:styled-content>). Most of them are involved in antigen processing and presentation. However, induction of retinoic acid‐inducible gene (<jats:styled-content style="fixed-case">RIG</jats:styled-content>)‐I‐like receptors (<jats:styled-content style="fixed-case">RLR</jats:styled-content>) has not been investigated. Here we report that <jats:styled-content style="fixed-case">OSM</jats:styled-content> has the capability to induce the expression of the <jats:styled-content style="fixed-case">DE</jats:styled-content>xD/H‐Box <jats:styled-content style="fixed-case">RNA</jats:styled-content> helicases <jats:styled-content style="fixed-case">RIG</jats:styled-content>‐I and melanoma differentiation antigen 5 (<jats:styled-content style="fixed-case">MDA</jats:styled-content>5) as well as of the transcription factors interferon regulatory factor (<jats:styled-content style="fixed-case">IRF</jats:styled-content>)1, <jats:styled-content style="fixed-case">IRF</jats:styled-content>7 and <jats:styled-content style="fixed-case">IRF</jats:styled-content>9 in primary fibroblasts. Induction of the helicases depends on tyrosine as well as serine phosphorylation of <jats:styled-content style="fixed-case">STAT</jats:styled-content>1. Moreover, we could show that the <jats:styled-content style="fixed-case">OSM</jats:styled-content>‐induced <jats:styled-content style="fixed-case">STAT</jats:styled-content>1 phosphorylation is predominantly counter‐regulated by a strong <jats:styled-content style="fixed-case">STAT</jats:styled-content>3‐dependent <jats:styled-content style="fixed-case">SOCS</jats:styled-content>3 induction, as <jats:italic>Stat3</jats:italic> as well as <jats:italic>Socs3</jats:italic> knock‐down results in an enhanced and prolonged helicase and <jats:styled-content style="fixed-case">IRF</jats:styled-content> expression. Other factors involved in regulation of <jats:styled-content style="fixed-case">STAT</jats:styled-content>1 or <jats:styled-content style="fixed-case">IRF</jats:styled-content>1 activity, like protein tyrosine phosphatase, non‐receptor type 2 (<jats:styled-content style="fixed-case">PTPN</jats:styled-content>2), promyelocytic leukaemia protein (<jats:styled-content style="fixed-case">PML</jats:styled-content>) or small ubiquitin‐related modifier 1 (<jats:styled-content style="fixed-case">SUMO</jats:styled-content>1), play a minor role in <jats:styled-content style="fixed-case">OSM</jats:styled-content>‐mediated induction of <jats:styled-content style="fixed-case">RLR</jats:styled-content>. Remarkably, <jats:styled-content style="fixed-case">OSM</jats:styled-content> and interferon‐γ (<jats:styled-content style="fixed-case">IFN</jats:styled-content>‐γ) synergize to mediate transcription of <jats:styled-content style="fixed-case">RLR</jats:styled-content> and pre‐treatment of fibroblasts with <jats:styled-content style="fixed-case">OSM</jats:styled-content> fosters the type I interferon production in response to a subsequent encounter with double‐stranded <jats:styled-content style="fixed-case">RNA</jats:styled-content>. Together, these findings suggest that the <jats:styled-content style="fixed-case">OSM</jats:styled-content>‐induced <jats:styled-content style="fixed-case">JAK</jats:styled-content>/<jats:styled-content style="fixed-case">STAT</jats:styled-content>1 signalling is implicated in virus protection of non‐professional immune cells and may cooperate with interferons to enhance <jats:styled-content style="fixed-case">RLR</jats:styled-content> expression in these cells.</jats:p>
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