Oncostatin M causes VEGF release from human airway smooth muscle: synergy with IL-1beta

Am J Physiol Lung Cell Mol Physiol. 2005 Jun;288(6):L1040-8. doi: 10.1152/ajplung.00333.2004. Epub 2005 Jan 21.


Vascular endothelial growth factor (VEGF), a potent angiogenesis factor, likely contributes to airway remodeling in asthma. We sought to examine the effects and mechanism of action of IL-6 family cytokines on VEGF release from human airway smooth muscle (HASM) cells. Oncostatin M (OSM), but not other IL-6 family cytokines, increased VEGF release, and IL-1beta enhanced OSM-induced VEGF release. OSM increased VEGF mRNA expression and VEGF promoter activity, whereas IL-1beta had no effect. IL-1beta did not augment the effects of OSM on VEGF promoter activity but did augment OSM-induced VEGF mRNA expression and mRNA stability. The STAT3 inhibitor piceatannol decreased both OSM-induced VEGF release and synergy between OSM and IL-1beta, without affecting responses to IL-1beta alone. Piceatannol also inhibited OSM-induced VEGF mRNA expression. In contrast, inhibitors of MAPK pathway had no effect on OSM or OSM plus IL-1beta-induced VEGF release. OSM increased type 1 IL-1 receptor (IL-1R1) mRNA expression, as measured by real-time PCR, and piceatannol attenuated this response. Consistent with the increase in IL-1R1 expression, OSM markedly augmented IL-1beta-induced VEGF, MCP-1, and IL-6 release. In summary, our data indicate OSM causes VEGF expression in HASM cells by a transcriptional mechanism involving STAT3. IL-1beta also synergizes with OSM to increase VEGF release, likely as a result of effects of IL-1beta on VEGF mRNA stability as well as effects of OSM on IL-1R1 expression. This is the first description of a role for OSM on IL-1R1 expression in any cell type. OSM may contribute to airway remodeling observed in chronic airway disease.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • DNA-Binding Proteins / antagonists & inhibitors
  • Drug Synergism
  • Enzyme Inhibitors / pharmacology
  • Growth Inhibitors / pharmacology*
  • Humans
  • Inflammation Mediators / pharmacology
  • Interleukin-1 / pharmacology*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lung / cytology
  • Lung / drug effects*
  • Lung / metabolism
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Muscle, Smooth / cytology
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Oncostatin M
  • Peptides / pharmacology*
  • Phosphorylation / drug effects
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-1 / metabolism
  • Receptors, Interleukin-1 Type I
  • STAT3 Transcription Factor
  • Signal Transduction
  • Stilbenes / pharmacology
  • Trans-Activators / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*


  • CCL2 protein, human
  • Chemokine CCL2
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Growth Inhibitors
  • Inflammation Mediators
  • Interleukin-1
  • Interleukin-6
  • OSM protein, human
  • Peptides
  • RNA, Messenger
  • Receptors, Interleukin-1
  • Receptors, Interleukin-1 Type I
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stilbenes
  • Trans-Activators
  • Vascular Endothelial Growth Factor A
  • Oncostatin M
  • 3,3',4,5'-tetrahydroxystilbene
  • Protein-Tyrosine Kinases
  • Mitogen-Activated Protein Kinases