Budesonide And TGF-β Synergize In Augmenting The Expression Of Fibronectin By Human Bronchial Epithelial Cells And Fetal Lung Fibroblasts

Object To investigate the effect of Budesonide on transforming growth factorβaugmented release of fibronectin (fn) by human fetal lung fibroblasts and human bronchial epithelial cells.Method Human bronchial epithelial cells which were harvestd from transplanted and human fetal lung fibroblasts were passaged and cultured to confluence in humidified 5% CO₂/ 95% air at 37℃in 100 mm tissue culture dishes, 1×10⁵ cells inoculated in 12-well tissue culture plates after trypsinization. cells were growth-arrested in serum/growth factor-deprived media for 24 hr before experiments. Immediately before each experiment, fresh serum/growth factor-free media containing TGF-βisoformsβ1,β2,β3, budesonide or the combination of those compounds were added, HFL-1 fibroblasts were incubated for 48 hr with budesonide alone or of either TGF-β2 orβ3 together with various concentrations of budesonide. Human bronchial epithelial cells were incubated for 24 hr with growth factor-free media containing TGF-β1, TGF-β2 or TGF-β3 in the absence or presence of various concentrations of budesonide. Post-culture media were collected for the assay of fn by Elisa.Result HFL-1 fibroblasts were incubated for 48 hr in serum-free media with various concentrations of budesonide, The effect of budesonide was assessed on basal Fn release by fibroblasts, Budesonide had significant effect on Fn release by fibroblasts over 48 hr incubation (p <0.05 vs control), significantly increased Fn release at 48 hr (p <0.05) by HFL-1 fibroblasts incubated with TGF-β2 or TGF-β3. The effect of budesonide on Fn release by HFL-1 fibroblasts is concentration dependent. When human bronchial epithelial cells were incubated for 24 hr with TGF-β1, TGF-β2, TGF-β3 in the absence or presence of budesonide, Budesonide, TGF-β1, TGF-β2 or TGF-β3 individually increased Fn release over 24 hr incubation, After the incubation with both budesonide with TGF-β1, TGF-β2, TGF-β3, fn release by HBECs further increased when compared with that stimulated with budesonide alone.Conclusion Budesonide and TGF-βs both increase the release of Fn by HFL-1 fibroblasts and HBECs. Futhermore, Budesonide synergistically increases TGF- P s-augmented release of HFL-1 fibroblasts and HBECs. The above results suggest a possible mechanism that glucocorticoids had little effect on late stage of pulmonary fibrosis and airway remodeling.