The effect of transforming growth factor (TGF)-β 1 and (TGF)-β 2 on nasal polyp fibroblast activities involved upper airway remodeling: Modulation by fluticasone propionate

Abstract

Transforming growth factor (TGF)-β may play a significant role in nasal polyposis pathogenesis, possibly through fibroblast activation. We studied the effects of two TGF-β isoforms (TGF-β 1 and TGF-β 2) on nasal polyposis fibroblasts by evaluating cell proliferation and differentiation into myofibroblasts. In addition, the inhibitory activity of different concentrations of fluticasone propionate (F.P.) was tested in this in vitro system. Primary nasal polyp tissue-derived fibroblasts were stimulated with different concentrations (1, 10 and 20 ng/ml) of TGF-β 1 and TGF-β 2 for different incubation periods (24, 48 and 72 h) and cell proliferation [ 3H thymidine ([ 3H]TdR) incorporation] and α-smooth muscle actin (α-SMA) expression (immunocytochemistry) was evaluated. The lowest concentration of TGF-β 1 (1 ng/ml) induced a significant increase in [ 3H]TdR incorporation at 48 and 72 h ( p < 0.05, each comparison), while in the presence of TGF-β (10 ng/ml) and TGF-β 2 (1 ng/ml) the enhancement in cell proliferation was significant only after 48 h ( p < 0.05, each comparison with the unstimulated cells). In contrast, a significant increase in α-SMA expression was observed in the presence of the two highest concentration of both TGF-β isoforms, at 48 and 72 h for TGF-β 1 ( p < 0.05, each comparison), but only at 72 h for TGF-β 2 (<0.05, each comparison). Finally, at all concentrations tested, F.P. significantly inhibited the TGF-β 1 and TGF-β 2-induced 3HTdR incorporation ( p < 0.01, each comparison) and the α-SMA expression ( p < 0.05, each comparison). Thus, in vitro different concentrations of TGF-β 1 and TGF-β 2 appear to sequentially stimulate primary nasal polyp tissue-derived fibroblast proliferation and myofibroblast differentiation. These activities are effectively inhibited by F.P.