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J Allergy Clin Immunol. 2003 Jun;111(6):1307-18.

TH2 Cytokine-enhanced and TGF-beta-enhanced vascular endothelial growth factor production by cultured human airway smooth muscle cells is attenuated by IFN-gamma and corticosteroids.

Author information

1
Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, 985125 Nebraska Medical Center, Omaha, NE 68198-5125, USA.

Abstract

BACKGROUND:

T(H)2 and T(H)1 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 T(H)2 cytokines (IL-4, IL-5, IL-10, and IL-13); transforming growth factor (TGF)-beta1, TGF-beta2, or TGF-beta3; and IL-1beta or TNF-alpha with or without IFN-gamma. Budesonide and exogenous prostaglandin (PG)E(2) were also evaluated. Postculture media were assayed for VEGF and PGE(2) 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-gamma 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-beta isoforms augmented VEGF production, which was reduced by IFN-gamma (P <.005). IL-1beta also increased VEGF production, but this was not affected by IFN-gamma (P >.05). TNF-alpha alone had little effect on VEGF release by ASMC. Production of VEGF stimulated by all cytokines was inhibited by budesonide. Exogenous PGE(2) increased VEGF release, but cytokine modulation of PGE(2) release did not always correlate with VEGF release.

CONCLUSIONS:

T(H)2 cytokines and TGF-beta stimulate ASMC release of VEGF. This can be inhibited by IFN-gamma and glucocorticoids.

PMID:
12789234
DOI:
10.1067/mai.2003.1455
[Indexed for MEDLINE]

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