Interaction between oncostatin M, interleukin 1 and prostaglandin E2 in induction of IL-6 expression in human fibroblasts

Cytokine. 1994 Jan;6(1):40-7. doi: 10.1016/1043-4666(94)90006-x.


The role of Oncostatin M (OM), a monocyte/macrophage and T-cell product, in regulating IL-6 expression in fibroblasts of lung or synovial origin was examined in vitro. Although by itself OM had a minimal effect on enhancing IL-6 production by fibroblasts, in combination with IL-1 alpha or PGE2, OM addition resulted in a dose-dependent synergistic enhancement of IL-6 production. This synergistic effect with either IL-1 alpha (5 ng/ml) or PGE2 (10(-7) M) was clearly evident at concentrations of OM of 10, 20 or 50 ng/ml. Levels of IL-6 resulting from OM and IL-1 alpha stimulation could be reduced by indomethacin (10(-6) M) and restored again by also adding PGE2. Northern blots probed for IL-6 mRNA showed cooperative enhancement of steady state levels at 18 hours of stimulation by OM and IL-1 alpha, or OM and PGE2. Probing for mRNA of the metalloproteinase inhibitor TIMP-1 showed that stimulation by OM, IL-1 alpha or PGE2 enhanced TIMP-1 levels. However, OM (alone) or PGE2 or both combined did not elevate the metalloproteinase stromelysin-1 mRNA signals. Analysis utilizing a rat IL-6 promoter-luciferase reporter gene construct showed that OM stimulation resulted in activation of transcription that synergistically enhanced IL-1-induced levels of reporter gene expression. These results show that although OM has minor effects on IL-6 production alone, the combination of OM and other mediators result in markedly enhanced IL-6 production by fibroblasts in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Assay
  • Blotting, Northern
  • Cell Line
  • Cytokines / pharmacology*
  • Dinoprostone / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Fibroblasts / drug effects
  • Fibroblasts / immunology
  • Fibroblasts / metabolism
  • Gene Expression / drug effects*
  • Glycoproteins / biosynthesis
  • Humans
  • Interleukin-1 / pharmacology*
  • Interleukin-6 / analysis
  • Interleukin-6 / biosynthesis*
  • Kinetics
  • Lung
  • Matrix Metalloproteinase 3
  • Metalloendopeptidases / biosynthesis
  • Oncostatin M
  • Peptides / pharmacology*
  • Promoter Regions, Genetic
  • RNA, Messenger / biosynthesis
  • Rats
  • Recombinant Fusion Proteins / analysis
  • Recombinant Fusion Proteins / biosynthesis
  • Synovial Membrane
  • Tissue Inhibitor of Metalloproteinases
  • Transcription, Genetic / drug effects
  • Transfection


  • Cytokines
  • Glycoproteins
  • Interleukin-1
  • Interleukin-6
  • OSM protein, human
  • Peptides
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Tissue Inhibitor of Metalloproteinases
  • Oncostatin M
  • Metalloendopeptidases
  • Matrix Metalloproteinase 3
  • Dinoprostone