Parabromophenacyl bromide inhibits subepithelial fibrosis by reducing TGF-β1 in a chronic mouse model of allergic asthma.

BACKGROUND Our previous study showed that parabromophenacyl bromide (PBPB) inhibits the features of allergic airway inflammation and airway hyperresponsiveness (AHR). However, its effect on airway remodeling, e.g. subepithelial fibrosis in a chronic allergic asthma model, was not investigated. We examined this issue in this study. METHODS PBPB was administered to mice with an induced chronic asthmatic condition. AHR was estimated at the end of the experiment, followed by euthanasia. Lung sections were stained with hematoxylin and eosin, periodic acid-Schiff and Masson's trichrome to determine airway inflammation, goblet cell metaplasia and subepithelial fibrosis, respectively. Transforming growth factor-β1 (TGF-β1) was estimated in lung homogenates. To determine the effect of PBPB on smooth-muscle hyperplasia, immunohistochemistry against α-smooth-muscle actin was performed on the lung sections. RESULTS Chronic ovalbumin challenges in a mouse model of allergic asthma caused significant subepithelial fibrosis and elevated TGF-β1, along with significant AHR. PBPB attenuated subepithelial fibrosis with a reduction of lung TGF-β1, airway inflammation and AHR without affecting goblet cell metaplasia. It also attenuated smooth-muscle hyperplasia with a reduction in the expression of α-smooth-muscle actin in the lungs. CONCLUSION Our findings indicate that PBPB attenuates some crucial features of airway remodeling such as subepithelial fibrosis and smooth-muscle hyperplasia. These data suggest that PBPB could therefore be a therapeutic drug for chronic asthma.