TGF-beta 1 modulates human airway smooth-muscle cell proliferation induced by mitogens.
Asthma is a disease of airway inflammation and bronchoconstriction that results in airway smooth-muscle cell hypertrophy and hyperplasia. The underlying mechanisms that induce myocyte proliferation remain unknown. Evidence suggests that cytokines such as transforming growth factor (TGF)-beta 1 may play a role in modulating this process. In this study, we examined the effects of TGF-beta 1 on human airway smooth-muscle (HASM) cell proliferation. We found that treatment of HASM cells with TGF-beta 1 inhibited epidermal growth factor (EGF)- and thrombin-induced DNA synthesis. This inhibition was both dose and time dependent. We then investigated whether these effects are mediated through activation of mitogen-activated protein kinase (MAP kinase), an enzyme that is thought to play a central role in the regulation of cell proliferation. We found that MAP kinase activation induced by EGF was not modulated by TGF-beta 1, despite TGF-beta 1 inhibiting EGF-induced HASM cell growth. These data suggest that TGF-beta 1 inhibits mitogen-induced HASM cell proliferation, but does so downstream from MAP kinase activation, or via a parallel pathway that is independent of MAP kinase activation.
Cohen
M D
MD
Pulmonary and Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, USA.
Ciocca
V
V
Panettieri
R A
RA
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D008934:Mitogens / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology; D014132:Trachea / Q000166:cytology* / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D008934:Mitogens; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D013917:Thrombin