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: Ya-Juan Chen, Tao Wang, Dai-Shun Liu, Dan Xu, Lei Chen, Jing An, Fu-Qiang Wen
• Journal: Cell biology international (Cell Biol Int) Vol. 34 Issue 7 Pg. 777-82 (Jul 2010) ISSN: 1095-8355 [Electronic] England
• PMID: 20359293 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucocorticoids
• Smad Proteins
• Transforming Growth Factor beta1
• Vascular Endothelial Growth Factor A
• Budesonide
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Budesonide (pharmacology)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Enzyme Activation
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Fibroblasts (cytology, drug effects, metabolism)
• Glucocorticoids (pharmacology)
• Humans
• Lung (cytology)
• Signal Transduction (drug effects)
• Smad Proteins (metabolism)
• Transforming Growth Factor beta1 (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)