A Time Course Study on the Development of Allergen-induced Nasal Airway Remodeling in a Rat Model

Abstract

Background Only a few studies have investigated the airway remodeling process in allergic rhinitis (AR), and the results reported are conflicting. We established an allergen-induced nasal remodeling model for AR using brown Norway rats and investigated time-dependent histological changes and the reversibility of the epithelial and subepithelial changes. Methods Ovalbumin (OVA)-sensitized rats were exposed to OVA daily and then assigned to one of five groups depending on the duration of the challenge. Groups I, II, III, and IV rats were exposed for 1, 4, 8, and 12 weeks, respectively. Group V rats were exposed for 12 weeks and then protected from challenge for 4 weeks. Matched control rats were exposed to saline. Histological parameters of the nasal mucosa such as epithelial and subepithelial thickness, goblet cell hyperplasia, eosinophil infiltration, submucosal gland hypertrophy, and expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were compared between groups. Results Repeated challenges for 12 weeks resulted in the characteristic features of nasal airway remodeling. All parameters except epithelial thickness increased markedly. Goblet cell hyperplasia and eosinophil infiltration decreased to control group levels after cessation of challenge for 4 weeks. Subepithelial changes such as subepithelial thickening, submucosal gland hypertrophy, and increased expression of MMP-9 and TIMP-1 were still observed after 4 weeks without challenge. Conclusion Our results indicate that prolonged OVA challenge can induce nasal remodeling. Epithelial changes were minimal or absent after cessation of the challenge, but subepithelial changes were resistant to reversal.