Effects of aminophylline on airway epithelial-mesenchymal transition in brown Norway rats after repeated allergen challenge

Purpose: Chronic asthma is characterized by airway inflammation and remodeling. The aim of this study is to evaluate the effects of aminophylline on airway epithelial-mesenchymal transition (EMT). Materials and methods: Two experimental groups of brown Norway rats that were repeatedly challenged with aerosolized ovalbumin (OA) were given oral aminophylline (OA-aminophylline group) or saline only (OA-saline group). A third group was challenged by saline as a control. The rats were anesthetized and pulmonary function were performed. Immuno-histochemical staining of epithelial markers (zonula occludens-1 (ZO-1)) and mesenchymal markers (vimentin) in the airway were performed. The protein expressions of ZO-1, E-cadherin, vimentin, fibronectine, TGF-ß1, SMAD 2/3, JNK, and p38 MAPK were examined by western blot. Results: Aminophylline had beneficial effects on airway inflammation, and airway remodeling in the OA-aminophylline group compared to the OA-saline group. The OA-saline group had decreased ZO-1 but increased vimentin according to immuno-histochemical staining. The protein expression indicated decreases in ZO-1 and E-cadherin but increases in vimentin, fibronectine, TGF-ß1, SMAD 2/3, JNK, and p38 MAPK in comparison to the other two groups. The OA-aminophylline group had higher ZO-1 but lower vimentin in immuno-histochemical staining compared to the OA-saline group. The protein expression showed higher ZO-1 and E-cadherin but lower vimentin, fibronectine, TGF-ß1, SMAD 2/3, JNK, and p38 MAPK when compared to the OA-saline group. Conclusions: Ovalbumin increases airway remodeling and airway EMT. Aminophylline is effective in preventing airway remodeling and airway EMT in Brown Norway rats after repeated allergen challenge.