TH2 cytokine-enhanced and TGF-β-enhanced vascular endothelial growth factor production by cultured human airway smooth muscle cells is attenuated by IFN-γ and corticosteroids

Fu Qiang Wen, Xiangde Liu, Winfred Manda, Yusuke Terasaki, Tetsu Kobayashi, Shinji Abe, Qiuhong Fang, Ronald Ertl, Lidia Manouilova, Stephen I. Rennard

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

Background: TH2 and TH1 cytokines have opposite effects on many aspects of the inflammatory response. Methods: This study was designed to determine if cytokines possibly present in asthma can modulate airway smooth muscle cell (ASMC) production of vascular endothelial growth factor (VEGF) and thus contribute to altered airway vascularity. ASMC were incubated for 24 hours with various concentrations of TH2 cytokines (IL-4, IL-5, IL-10, and IL-13); transforming growth factor (TGF)-β1, TGF-β2, or TGF-β3; and IL-1β or TNF-α with or without IFN-γ. Budesonide and exogenous prostaglandin (PG)E2 were also evaluated. Postculture media were assayed for VEGF and PGE2 by ELISA. Results: IL-4, IL-5, and IL-13 alone but not IL-10 enhanced VEGF production by ASMC in a concentration-dependent manner. IFN-γ alone inhibited spontaneous VEGF release by ASMC and concentration-dependently attenuated IL-4-augmented, IL-5-augmented, or IL-13-augmented production of VEGF (P < .01). All three TGF-β isoforms augmented VEGF production, which was reduced by IFN-γ (P < .005). IL-1β also increased VEGF production, but this was not affected by IFN-γ (P > .05). TNF-α alone had little effect on VEGF release by ASMC. Production of VEGF stimulated by all cytokines was inhibited by budesonide. Exogenous PGE2 increased VEGF release, but cytokine modulation of PGE2 release did not always correlate with VEGF release. Conclusions: TH2 cytokines and TGF-β stimulate ASMC release of VEGF. This can be inhibited by IFN-γ and glucocorticoids.

Original languageEnglish (US)
Pages (from-to)1307-1318
Number of pages12
JournalJournal of Allergy and Clinical Immunology
Volume111
Issue number6
DOIs
StatePublished - Jun 1 2003

Keywords

  • Corticosteroids
  • Human airway smooth muscle cells
  • T2/T1 cytokines
  • Transforming growth factor-β
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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