Effect Of Budesonide On TGF-beta1 Induced VEGF Production By Human Fetal Lung Fibroblasts

ObjectiveAirway remodeling and lung fibrosis are the leading causes result in increasingly high mutilation and mortality in respiratory disease. Studies show that inflammatory tissue damage and inappropriate repair lead to bronch-lung fibrosis, in which angiogenesis relating growth factors maybe involved. In the current study, we examined the effect of budesonide on transforming growth factor-β1 (TGF-β1) induced vascular endothelial growth factor (VEGF) release by human fetal lung fibroblast (HFL-1).MethodsBy using cultured human fetal lung fibroblasts, we firstly examed the time-dependency of TGF-Bl induced VEGF production by human fetal lung fibroblasts. HFL-1 fibroblasts treated with 0.25ng/ml TGF-β1 were incubated for 12, 24, 48 and 72 hrs.The post-culture media were collected for enzyme immunoassay ( EIA) of VEGF. Cell counts were also done.Secondly, we examed the dose-dependency of TGF-Bl induced VEGF production by human fetal lung fibroblasts. HFL-1 fibroblasts were cultured with various concentrations of TGF-β1 for 72 hrs.The post-culture media were collected for EIA.Finally, we examed the effect of Budesonide on basal and TGF-β1 induced VEGF release by HFL-1 fibroblasts. HFL-1 fibroblasts were treated with various concentrations of budesonide in the absence and presence of 0.5ng/ml TGF-β1 for 72 hrs. Post-culture media were collected for the assay of VEGF at 72 hrs.ResultsHFL-1 fibroblasts increasingly release VEGF as incubation goes on. With the stimulation of TGF-β1, increased release of VEGF was noted at different time points.A significant increase in VEGF was observed in HFL-1 fibroblasts treated with 0. 5-5ng/ml of TGF-β1 ( P<0.05). A sevenfold increase in VEGF release was observed in cells treated with 5ng/ml TGF-β1 compared with control. However, cells treated with TGF-β1 below 0.5ng/ml had no stimulatory effect on VEGF release by HFL-1 fibroblasts.10^-7M of Budesonide significantly decreased VEGF release by HFL-1 cells. Furthermore, TGF-81 argumented release of VEGF was attenuated by Bud at 10^-9M and 10^-7M, which shows a dose-dependent manner.ConclusionsHFL-1 fibroblasts release VEGF spontaneously. TGF-β1 increased the release of VEGF by HFL-1 fibroblasts in a time and dose-dependent manners. Budesonide inhibited basal VEGF release, and TGF-β1 enhanced VEGF production by HFL-1 fibroblast. Suppession of VEGF production may be a mechanism that budesonide modulates fibroblasts' function in pulmonary fibrosis.