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

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.