Dexamethasone Attenuates PDGF- and TGF-beta-enhanced Vascular Endothelial Growth Factor Production in Cultured Human Bronchial Smooth Muscle Cells / 소아알레르기및호흡기학회지

ABSTRACT

PURPOSE: Human bronchial smooth muscle cell(HBSMC) plays an important role in the remodeling of the airways in asthma. Vascular endothelial growth factor(VEGF) is a multifunctional cytokine, which induces edema, angiogenesis, vascular remodeling, mucus metaplasia, subepithelial fibrosis, and antigen-induced Th2 inflammation. Transforming growth factor-beta(TGF-beta) is a growth modulator of HBSMC and an important cytokine in airway remodeling. We investigated the effect of dexamethasone on the release of VEGF from HBSMC stimulated with platelet-derived growth factor(PDGF) and TGF-beta. METHODS: HBSMC cultured in 10 percent FCS-DMEM media was growth-arrested in serum-deprived medium for 48 hours. Dexamethasone and TGF-beta were added and incubated for 16 hours before stimulation with PDGF. After 24 hours of stimulation, culture medium was harvested and stored at -80 degrees C until ELISA for VEGF was performed. RESULTS: The release of VEGF was significantly increased after stimulation with PDGF (P<0.01). The production of VEGF pretreated with TGF-beta before stimulation with PDGF was higher than those without TGF-beta pretreatment(P<0.01). Dexamethasone suppressed the release of VEGF in HBSMC stimulated with PDGF(P<0.01), TGF-beta and PDGF(P<0.01). CONCLUSION: PDGF and TGF-beta may be one of the key mediators in inducing airway remodeling and glucocorticoid, and can be used as useful therapies to prevent airway vascular remodeling by modulating the VEGF on airway smooth muscle cells.