The effects of salbutamol, beclomethasone, and dexamethasone on fibronectin expression by cultured airway smooth muscle cells.
Possible mechanisms of adverse drug effects in asthma include worsening of cellular hyperplasia and stimulation of extracellular matrix deposition. In this study, salbutamol, dexamethasone and beclomethasone were investigated to ascertain their ability to induce mitogenesis and stimulate fibronectin expression in cultured canine airway smooth muscle cells. In cells maintained in serum-free media for 72 h, salbutamol (1 nM-10 microM) caused mitogenesis. The control cells had 2.57 +/- 0.34 x 10(5) cells per ml (mean +/- SEM, N = 13), while salbutamol (1 microM) caused a maximal increase in cell number to 3.57 +/- 0.23 x 10(5) cells/ml (P < 0.01). In cells stimulated to replicate by addition of either fetal bovine serum or canine serum, no additional mitogenic effect of salbutamol was seen. Salbutamol did not have a detectable quantitative effect on fibronectin matrix expression. The glucocorticoids, beclomethasone and dexamethasone, significantly altered fibronectin expression by cultured airway smooth muscle cells. Beclomethasone increased fibronectin expression, while dexamethasone decreased expression.
Shiels
I A
IA
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
Bowler
S D
SD
Taylor
S M
SM
D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D001507:Beclomethasone / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004285:Dogs; D005353:Fibronectins / Q000096:biosynthesis / Q000378:metabolism*; D007150:Immunohistochemistry; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D014132:Trachea / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism
D005353:Fibronectins; D003907:Dexamethasone; D001507:Beclomethasone; D000420:Albuterol