Figure 4

Simvastatin profoundly suppresses the augmented TGFβ1-induced fibronectin expression in asthmatic bronchial fibroblasts. Western analysis was performed using whole cell lysates obtained from nonasthmatic and asthmatic bronchial fibroblast cultures that were maintained under TGFβ1 (2.5 ng/ml)-stimulated or serum-deprived conditions in the absence or presence of simvastatin (0.1-10 μM) for 48 h. (A) Western blots showing simvastatin dose-dependently suppresses TGFβ1-induced fibronectin expression in nonasthmatic and asthmatic bronchial fibroblasts, whereas GGTase 1β and FTase β protein abundance is not affected. (B) Representative western blot showing a more robust TGFβ1-induced fibronectin abundance in asthmatic versus nonasthmatic fibroblasts, which is effectively suppressed by simvastatin. (C) Densitometric analysis revealed significant differences in TGFβ1-induced fibronectin expression between nonasthmatic and asthmatic fibroblasts. Moreover, simvastatin markedly prevents fibronectin expression in both cell types. Data represent means ± s.e. mean of 5 independent experiments, using cells obtained from 3 non-asthmatic and 3 asthmatic subjects. Legend: t = 0: initial basal (unstimulated) cultures; t = 48 h: treatment time-matched, basal (unstimulated) cultures; Simv: simvastatin. **P < 0.01, ***P < 0.001 compared to asthmatic TGFβ. ^#P < 0.05, ^###P < 0.001 compared to nonasthmatic TGFβ.