Open AccessOncostatin M induces RIG‐I and MDA5 expression and enhances the double‐stranded RNA response in fibroblasts
Author(s) -
Hergovits Sabine,
Mais Christine,
Haan Claude,
CostaPereira Ana P.,
Hermanns Heike M.
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13221
Subject(s) - oncostatin m , biology , stat1 , rig i , interferon , microbiology and biotechnology , stat protein , interferon regulatory factors , rna helicase a , jak stat signaling pathway , transcription factor , phosphorylation , helicase , rna , stat3 , cytokine , receptor tyrosine kinase , gene , immunology , interleukin 6 , biochemistry
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 DE xD/H‐Box RNA helicases RIG ‐I and melanoma differentiation antigen 5 ( MDA 5) as well as of the transcription factors interferon regulatory factor ( IRF )1, IRF 7 and IRF 9 in primary fibroblasts. Induction of the helicases depends on tyrosine as well as serine phosphorylation of STAT 1. Moreover, we could show that the OSM ‐induced STAT 1 phosphorylation is predominantly counter‐regulated by a strong STAT 3‐dependent SOCS 3 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 STAT 1 or IRF 1 activity, like protein tyrosine phosphatase, non‐receptor type 2 ( PTPN 2), promyelocytic leukaemia protein ( PML ) or small ubiquitin‐related modifier 1 ( SUMO 1), 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 / STAT 1 signalling is implicated in virus protection of non‐professional immune cells and may cooperate with interferons to enhance RLR expression in these cells.