Effect of budesonide on TGF-beta1-enhanced VEGF production by lung fibroblasts.
VEGF (vascular endothelial growth factor) is a potent proangiogenic cytokine, and vascular change is one of the characteristic features of airway remodelling. Since the glucocorticoids have shown antifibrosis properties, we sought to investigate whether budesonide, a widely used glucocorticoid in clinical practice, could attenuate TGF-beta1 (transforming growth factor-beta1)-induced VEGF production by HFL-1 (human lung fibroblasts). HFL-1 fibroblasts were treated with various concentrations of budesonide (10(-11) M, 10(-9) M and 10(-7) M) in the absence or presence of TGF-beta1. Postculture media were collected for ELISA of VEGF at the indicated times. The cell lysates were subjected to Western blotting analysis to test TGF-beta1/Smad and MAP (mitogen-activated protein) kinase signalling activation, respectively. The results suggested that budesonide pretreatment reduced the significant increase of VEGF release induced by TGF-beta1 in HFL-1 fibroblasts in a dose-dependent manner, and suppressed the increase of phospho-Smad3 and phosphor-ERK (extracellular signal-regulated kinase) protein levels. In conclusion, budesonide may reduce TGF-beta1-induced VEGF production in the lung, probably through the Smad/ERK signalling pathway and, thus, may provide new sight into the molecular mechanism underlying glucocorticoid therapy for airway inflammatory diseases.
Chen
Ya-Juan
YJ
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, Peoples Republic of China.
Wang
Tao
T
Liu
Dai-Shun
DS
Xu
Dan
D
Chen
Lei
L
An
Jing
J
Wen
Fu-Qiang
FQ
D000818:Animals; D019819:Budesonide / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000166:cytology*; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D005938:Glucocorticoids; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D019819:Budesonide; D048049:Extracellular Signal-Regulated MAP Kinases