title: Effect of budesonide on TGF-beta1-enhanced VEGF production by lung fibroblasts.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Dai-Shun
authors.initials: DS
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: An
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Wen
mesh_terms: 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*
chemical_list: D005938:Glucocorticoids; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D019819:Budesonide; D048049:Extracellular Signal-Regulated MAP Kinases