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

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Title: Oncostatin M induces RIG-I and MDA5 expression and enhances the double-stranded RNA response in fibroblasts
Authors: Hergovits, S
Mais, C
Haan, C
Costa-Pereira, AP
Hermanns, HM
Item Type: Journal Article
Abstract: Interleukin (IL)-6-type cytokines have no direct antiviral activity; nevertheless, they display immune-modulatory functions. Oncostatin M (OSM), a member of the IL-6 family, has recently been shown to induce a distinct number of classical interferon stimulated genes (ISG). Most of them are involved in antigen processing and presentation. However, induction of retinoic acid-inducible gene (RIG)-I-like receptors (RLR) has not been investigated. Here we report that OSM has the capability to induce the expression of the DExD/H-Box RNA helicases RIG-I and melanoma differentiation antigen 5 (MDA5) as well as of the transcription factors interferon regulatory factor (IRF)1, IRF7 and IRF9 in primary fibroblasts. Induction of the helicases depends on tyrosine as well as serine phosphorylation of STAT1. Moreover, we could show that the OSM-induced STAT1 phosphorylation is predominantly counter-regulated by a strong STAT3-dependent SOCS3 induction, as Stat3 as well as Socs3 knock-down results in an enhanced and prolonged helicase and IRF expression. Other factors involved in regulation of STAT1 or IRF1 activity, like protein tyrosine phosphatase, non-receptor type 2 (PTPN2), promyelocytic leukaemia protein (PML) or small ubiquitin-related modifier 1 (SUMO1), play a minor role in OSM-mediated induction of RLR. Remarkably, OSM and interferon-γ (IFN-γ) synergize to mediate transcription of RLR and pre-treatment of fibroblasts with OSM fosters the type I interferon production in response to a subsequent encounter with double-stranded RNA. Together, these findings suggest that the OSM-induced JAK/STAT1 signalling is implicated in virus protection of non-professional immune cells and may cooperate with interferons to enhance RLR expression in these cells.
Issue Date: 30-May-2017
Date of Acceptance: 3-Apr-2017
URI: http://hdl.handle.net/10044/1/49313
DOI: https://dx.doi.org/10.1111/jcmm.13221
ISSN: 1582-4934
Publisher: Wiley
Start Page: 3087
End Page: 3099
Journal / Book Title: Journal of Cellular and Molecular Medicine
Volume: 21
Issue: 11
Copyright Statement: © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: DExD/H-Box RNA helicase
RIG-I
STAT1
innate immunity
oncostatin M
0304 Medicinal And Biomolecular Chemistry
0601 Biochemistry And Cell Biology
1103 Clinical Sciences
Biochemistry & Molecular Biology
Publication Status: Published
Appears in Collections:Department of Surgery and Cancer