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

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. 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. 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. 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.

Ram A ，Mabalirajan U ，Jaiswal A ，Rehman R ，Singh VP ，Ghosh B ... -  《-》

Inhibition airway remodeling and transforming growth factor-β1/Smad signaling pathway by astragalus extract in asthmatic mice.

Qu ZH ，Yang ZC ，Chen L ，Lv ZD ，Yi MJ ，Ran N ... -  《-》

Mepacrine inhibits subepithelial fibrosis by reducing the expression of arginase and TGF-beta1 in an extended subacute mouse model of allergic asthma.

Mabalirajan U ，Aich J ，Agrawal A ，Ghosh B ... -  《-》

Intranasally administered serelaxin abrogates airway remodelling and attenuates airway hyperresponsiveness in allergic airways disease.

The peptide hormone relaxin plays a key role in the systemic hemodynamic and renovascular adaptive changes that occur during pregnancy, which is linked to its antiremodelling effects. Serelaxin (a recombinant form of human gene-2 relaxin) has been shown to inhibit lung fibrosis in various disease models and reverse airway remodelling and airway hyperresponsiveness (AHR) in allergic airways disease (AAD). Although continuous systemic delivery of exogenous serelaxin alleviates allergic fibrosis and AHR, more direct routes for administration into the lung have not been investigated. Thus, intranasal administration of serelaxin was evaluated for its ability to reverse airway remodelling and AHR associated with AAD. Female Balb/c mice were subjected to a 9-week model of chronic AAD. Subgroups of animals (n = 12/group) were then treated intranasally with serelaxin (0.8 mg/mL) or vehicle once daily for 14 days (from weeks 9-11). Saline-sensitized/challenged mice treated with intranasal saline served as additional controls. Differential bronchoalveolar lavage (BAL) cell counts, ovalbumin (OVA)-specific IgE levels, tissue inflammation, parameters of airway remodelling and AHR were then assessed. Chronic AAD was associated with significant increases in differential BAL cell counts, OVA-specific IgE levels, inflammation, epithelial thickening, goblet cell metaplasia, TGF-β1 expression, epithelial Smad2 phosphorylation (pSmad2), subepithelial collagen thickness, total lung collagen concentration and AHR (all P < 0.05 vs. respective measurements from saline-treated mice). Daily intranasal delivery of serelaxin significantly diminished AAD-induced epithelial thickening, epithelial pSmad2, subepithelial and total lung collagen content (fibrosis) and AHR (all P < 0.05 vs. vehicle-treated AAD mice). Intranasal delivery of serelaxin can effectively reduce airway remodelling and AHR, when administered once daily. Respirable preparations of serelaxin may have therapeutic potential for the prevention and/or reversal of established airway remodelling and AHR in asthma.

Royce SG ，Lim CX ，Patel KP ，Wang B ，Samuel CS ，Tang ML ... -  《-》

Bangpungtongseong-san, a traditional herbal medicine, attenuates chronic asthmatic effects induced by repeated ovalbumin challenge.

Lee MY ，Shin IS ，Jeon WY ，Shin N ，Shin HK ... -  《-》