Airway smooth muscle hyperplasia, which may be induced by growth factors (platelet-derived growth factor, PDGF; transforming growth factor-alpha, TGF-alpha; insulin like growth factor, IGF) has been a characteristic finding in the bronchi of patients with chronic asthma. The precise mechanism that induce airway smooth muscle hypcrplasia remains unknown. Recently our laboratory has shown that A1 adenosinc receptor activation appears to play in important role in modulating airway hyperresponsiveness in a rabbit model of allergic asthma.Therefore, this study was designed to determine the eflect of PDGF, TGF-alpha and IGF on adenosine receptors (A1 & A2) as well as expression and stimulation of proliferation of human airway smooth muscle (HASM) cells. A1 receptor binding was performed after the treatment of HASM cells with PDGF (20ng/ml), IGF (20ng/ml) and TGF-alpha (20ng/ml) using specific A1 receptor antagonist [3H]DPCPX. A2 receptors binding studies using a relatively specific A2 receptor agonist [125I]PAPA-APEC were performed in HASM cells after the treatment of growth factors. The results are presented below: % Spécifie bindini/ut/proteln CanlEil £B£E IGE TCP-alpha A1 receptor 14.7±1.0 12.2±1.5 12.7±1.5 16.5±1.7 A2 receptor 30.6±1.4 11.7±0.6 13.8±1.3 10.7±0.6 Growth factors appear to decrease specific- ligand binding to A, receptors significantly (P<0.05)but has little effect on modulating ligand binding to A, receptors. The proliferation rate was determined by seeding (15×105) cells in culture dishes in the normal medium. After 12 hours, these cells were washed and treated with growth factors in free-FBS culturing medium. The total number of cells were counted after 24 hours. The number of cells were significantly (P<0.05) increased after the treatment with PDGF, IGF and TGF-alpha. This study show that growth factors may play a role in the alternation of adenosine receptors and may ofler insight into the role of PDGF, IGF and TGF-alpha in asthma in modulating ASM responses to adenosine .
|Original language||English (US)|
|State||Published - 1996|
All Science Journal Classification (ASJC) codes
- Molecular Biology