title: 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.
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.
authors.affiliation: Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, 985125 Nebraska Medical Center, Omaha, NE 68198-5125, USA.
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Wen
authors.forename: Xiangde
authors.initials: X
authors.lastname: Liu
authors.forename: Winfred
authors.initials: W
authors.lastname: Manda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Terasaki
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Abe
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Fang
authors.forename: Ronald
authors.initials: R
authors.lastname: Ertl
authors.forename: Lidia
authors.initials: L
authors.lastname: Manouilova
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019819:Budesonide / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D008168:Lung / Q000166:cytology*; D008222:Lymphokines / Q000096:biosynthesis*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D008222:Lymphokines; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019819:Budesonide; D007371:Interferon-gamma; D015232:Dinoprostone