Budesonide reduces vascular endothelial growth factor secretion and expression in airway (Calu-1) and alveolar (A549) epithelial cells

Eur J Pharmacol. 2001 Aug 10;425(2):109-16. doi: 10.1016/s0014-2999(01)01192-x.


Vascular endothelial growth factor (VEGF), a cytokine expressed in the respiratory epithelial cells, induces vascular hyperpermeability and edema, symptoms that are alleviated by budesonide, an anti-asthma corticosteroid. However, modulation of VEGF levels by budesonide in the respiratory epithelium has not been studied. In this study, we investigated the mechanisms of VEGF secretion using brefeldin A and monensin in human airway (Calu-1) and alveolar (A549) epithelial cells, and further determined whether budesonide inhibits VEGF secretion and mRNA expression through a glucocorticoid receptor-mediated mechanism. In both cell types, VEGF secretion was inhibited by brefeldin A and monensin, suggesting vesicular transport of VEGF through endoplasmic reticulum (ER)-golgi pathway. At concentrations devoid of cytotoxicity, budesonide reduced VEGF secretion and VEGF mRNA expression in both cell types and these effects were inhibited by mifepristone (RU 486), a glucocorticoid receptor antagonist, suggesting that budesonide reduces VEGF secretion and expression through its glucocorticoid receptor-mediated action. Also, budesonide-mediated inhibition of VEGF mRNA was time- and protein synthesis-dependent. Thus, budesonide may be of potential value in treating disorders of the respiratory tract that are associated with VEGF elevation.

MeSH terms

  • Administration, Topical
  • Anti-Inflammatory Agents / pharmacology
  • Bronchi / cytology
  • Bronchi / metabolism
  • Budesonide / pharmacology*
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / metabolism*
  • Glucocorticoids
  • Humans
  • Lymphokines / drug effects
  • Lymphokines / genetics
  • Lymphokines / metabolism*
  • Protein Synthesis Inhibitors / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / drug effects
  • Receptors, Glucocorticoid / drug effects
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism
  • Time Factors
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Anti-Inflammatory Agents
  • Endothelial Growth Factors
  • Glucocorticoids
  • Lymphokines
  • Protein Synthesis Inhibitors
  • RNA, Messenger
  • Receptors, Glucocorticoid
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Budesonide