Oncostatin M decreases interleukin-1 β secretion by human synovial fibroblasts and attenuates an acute inflammatory reaction in vivo

J Cell Mol Med. 2012 Jun;16(6):1274-85. doi: 10.1111/j.1582-4934.2011.01412.x.

Abstract

Oncostatin M (OSM) is a pleiotropic cytokine of the IL-6 family and displays both pro-inflammatory and anti-inflammatory activities. We studied the impact of OSM on the gene activation profile of human synovial cells, which play a central role in the progression of inflammatory responses in joints. In synovial cells stimulated with lipopolysaccharide and recombinant human granulocyte-macrophage colony-stimulating factor, recombinant human OSM and native OSM secreted by human granulocytes both reduced the gene expression and secretion of IL-1β and CXCL8, but increased that of IL-6 and CCL2. This impact on synovial cell activation was not obtained using IL-6 or leukaemia inhibitory factor. Signal transducer and activator of transcription-1 appeared to mediate the effects of OSM on stimulated human synovial fibroblasts. In the murine dorsal air pouch model of inflammation, OSM reduced the expression of the pro-inflammatory cytokines IL-1β and TNF-α in lining tissues, and their presence in the cavity. These results as a whole suggest an anti-inflammatory role for OSM, guiding inflammatory processes towards resolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Fibroblasts / drug effects*
  • Gene Expression Profiling
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Leukemia Inhibitory Factor / genetics
  • Leukemia Inhibitory Factor / metabolism
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Oncostatin M / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Synovial Fluid / cytology
  • Synovial Fluid / drug effects*
  • Synovial Fluid / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CCL2 protein, human
  • CXCL8 protein, human
  • Chemokine CCL2
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • Lipopolysaccharides
  • OSM protein, human
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Oncostatin M
  • Granulocyte-Macrophage Colony-Stimulating Factor