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.
Bandi
N
N
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198-6025, USA.
Kompella
U B
UB
D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D019819:Budesonide / Q000494:pharmacology*; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D005938:Glucocorticoids; D006801:Humans; D008222:Lymphokines / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000893:Anti-Inflammatory Agents; D016228:Endothelial Growth Factors; D005938:Glucocorticoids; D008222:Lymphokines; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019819:Budesonide