Oncostatin M causes VEGF release from human airway smooth muscle: Synergy with IL-1β

Débora S. Faffe, Lesley Flynt, Matthew Mellema, Timothy R. Whitehead, Kerri Bourgeois, Reynold A. Panettieri, Eric S. Silverman, Stephanie A. Shore

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

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-1β enhanced OSM-induced VEGF release. OSM increased VEGF mRNA expression and VEGF promoter activity, whereas IL-1β had no effect. IL-1β 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-1β, without affecting responses to IL-1β alone. Piceatannol also inhibited OSM-induced VEGF mRNA expression. In contrast, inhibitors of MAPK pathway had no effect on OSM or OSM plus IL-1β-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-1β-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-1β also synergizes with OSM to increase VEGF release, likely as a result of effects of IL-1β 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume288
Issue number6 32-6
DOIs
StatePublished - Jun 2005
Externally publishedYes

Keywords

  • Interleukin-1 receptor 1
  • Interleukin-6
  • Monocyte chemoattractant protein-1
  • Piceatannol
  • Signal transducer and activator of transcription 3
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

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    Faffe, D. S., Flynt, L., Mellema, M., Whitehead, T. R., Bourgeois, K., Panettieri, R. A., Silverman, E. S., & Shore, S. A. (2005). Oncostatin M causes VEGF release from human airway smooth muscle: Synergy with IL-1β. American Journal of Physiology - Lung Cellular and Molecular Physiology, 288(6 32-6). https://doi.org/10.1152/ajplung.00333.2004