| Abstrakt: |
Fibrosis around the smooth muscle of asthmatic airway walls leads to irreversible airway obstruction. Bronchial epithelial cells release granulocyte/macrophage colony-stimulating factor (GM-CSF) in asthmatics and are in close proximity to airway smooth muscle cells (ASMC). The findings in this study demonstrate that GM-CSF induces confluent, prolonged, serum-deprived cultures of ASMC to increase expression of collagen I and fibronectin. GM-CSF also induced ASMC to increase the expression of transforming growth factor (TGF)-β receptors type I, II, and III (TβR-I, TβR-II, TβR-III), but had no detectable effect on the release of TGF-β1 by the same ASMC. The presence of GM-CSF also induced the association of TGF-β1 with TβR-III, which enhances binding of TGF-β1 to TβR-II. The induction of TβRs was parallel to the increased induction of phosphorylated Smad2 (pSmad2) and connective tissue growth factor (CTGF), indicative of TGF-βmediated connective tissue synthesis. Dexamethasone decreased GM-CSF-induced TβR-I, TβR-II, TβR-III, pSmad2, CTGF, collagen I, and fibronectin. In conclusion, GMCSF increases the responsiveness of ASMC to TGF-βl-mediated connective tissue expression by induction of TβRs, which is inhibited by corticosteroids. [ABSTRACT FROM AUTHOR] |
