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Oncostatin M acting via OSMR, augments the actions of IL-1 and TNF in synovial fibroblasts

In English

Författare

  • B. Le Goff
  • Sofie Singbrant
  • B. A. Tonkin
  • T. J. Martin
  • E. Romas
  • N. A. Sims
  • N. C. Walsh

Summary, in English

OBJECTIVE: To identify how the gp130-signaling cytokine oncostatin M (OSM), acting alone or in concert with IL-1beta or TNFalpha, affects synovial fibroblast expression of genes relevant to inflammation and bone erosion in inflammatory arthritis. METHODS: Synovial fibroblasts (SFs) were isolated from non-arthritic wild type (WT) or OSM receptor deficient (OSMR(-/-)) mice and stimulated with OSM, IL-1beta or TNFalpha and their combinations. Cytokine gene expression was assessed by quantitative RT-PCR. ELISA, flow cytometry and immunohistochemistry identified protein expression. Gene expression patterns were confirmed in SFs isolated from patients with osteoarthritis (OASFs) and rheumatoid arthritis (RASFs). RESULTS: Expression of OSM and its receptors, gp130, OSMR and LIFR, was increased in synovial tissue from the mouse antigen-induced arthritis model. In isolated WT mouse synovial fibroblasts OSM alone, or in synergy with IL-1beta, or together with TNFalpha, potently induced expression of the pro-inflammatory cytokine IL-6. OSM also induced a sustained increase in mRNA levels of the pro-osteoclastic cytokine RANKL. Combining OSM with IL-1beta, but not with TNFalpha, further increased RANKL expression. Importantly these effects of OSM were all dependent on the expression of OSMR. Furthermore, OSM also increased expression of its own receptors, gp130 and OSMR and the IL-1 receptor, IL1-R1; the latter effects were also observed in both human OASFs and RASFs. CONCLUSION: Together our data suggests that OSM signaling via OSMR in SFs has the potential to contribute significantly to joint destruction in inflammatory arthritis. It not only induces expression of pro-inflammatory and pro-osteoclastic cytokines but can also augment its own actions and that of IL-1 by inducing expression of OSMR and IL-1R1.

Publiceringsår

2014

Språk

Engelska

Sidor

9-101

Publikation/Tidskrift/Serie

Cytokine

Volym

68

Issue

2

Dokumenttyp

Artikel i tidskrift

Förlag

Academic Press

Ämne

  • Rheumatology and Autoimmunity

Nyckelord

  • Synovial Membrane/*pathology
  • Rheumatoid/genetics/pathology
  • Animals
  • Humans
  • Tumor Necrosis Factor-alpha/*metabolism
  • Arthritis
  • Il-1
  • Il-6
  • Oncostatin M
  • Synovial fibroblast
  • Interleukin-1beta/genetics/*metabolism
  • Receptors
  • Oncostatin M/deficiency/*metabolism
  • Inbred C57BL
  • Gene Expression Regulation
  • Mice
  • Oncostatin M/*metabolism
  • Fibroblasts/*metabolism
  • Osteoprotegerin/genetics/metabolism
  • RNA
  • Messenger/genetics/metabolism
  • RANK Ligand/genetics/metabolism
  • Interleukin-1/metabolism

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1096-0023