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 resp iratory epithelial cells, induces vascular hyperpermeability and edema, sym ptoms that are alleviated by budesonide, an anti-asthma corticosteroid. How ever, modulation of VEGF levels by budesonide in the respiratory epithelium has not been studied. In this study, we investigated the mechanisms of VEG F secretion using brefeldin A and monensin in human airway (Calu-1) and alv eolar (A549) epithelial cells, and further determined whether budesonide in hibits VEGF secretion and mRNA expression through a glucocorticoid receptor -mediated mechanism, In both cell types, VEGF secretion was inhibited by br efeldin A and monensin, suggesting vesicular transport of VEGF through endo plasmic reticulum (ER)-golgi pathway. At concentrations devoid of cytotoxic ity, budesonide reduced VEGF secretion and VEGF mRNA expression in both cel l types and these effects were inhibited by mifepristone (RU 486), a glucoc orticoid receptor antagonist, suggesting that budesonide reduces VEGF secre tion and expression through its glucocorticoid receptor-mediated action. Al so, budesonide-mediated inhibition of VEGF mRNA was time- and protein synth esis-dependent. Thus, budesonide may be of potential value in treating diso rders of the respiratory tract that are associated with VEGF elevation. (C) 2001 Elsevier Science B.V. All rights reserved.