The Serine Protease Inhibitor, 4-(2-aminoethyl) Benzene Sulfonyl Fluoride Hydrochloride, Reduces Allergic Inflammation in a House Dust Mite Allergic Rhinitis Mouse Model

motrypsin, plasmin, thrombin, kallikreins) and high affinity.AEBSF is a unique molecule that can inhibit serine proteases as well as NADPH oxidase, the primary enzyme responsible for catalyzing the production of reactive oxygen species in epithelial cells, inflammatory cells, and phagocytes. 5Due to these properties, we hypothesized that AEBSF might reduce allergic airway inflammation.Recently, it was reported that nafamostat mesilate, a potent serine protease inhibitor, inhibits airway eosinophilic inflammation and airway epithelial remodeling in a murine model of allergic asthma. 6Additionally, several serine Purpose: Serine protease inhibitors are involved in immune development, anti-inflammatory mechanisms, and tissue repair.In the present study, the serine protease inhibitor 4-(2-aminoethyl) benzene sulfonyl fluoride hydrochloride (AEBSF) was evaluated for its prophylactic and therapeutic applications in a mouse model of allergic rhinitis (AR).Methods: BALB/c mice were divided into 5 groups: contol (CON), Dermatophagoides farinae (Derf), AR mice treated with AEBSF before sensitization (S), AR mice treated with AEBSF after challenge (C), and steroid groups.Derf was used as an allergen.AEBSF was administered before S or after C. Allergic symptom scores, eosinophil counts, proteolytic activity, interferon-γ, interleukin (IL)-10 levels and serum Derf-specific IgE levels were measured.T-bet, GATA-3, Foxp3, IL-13, and transforming growth factor (TGF)-β mRNA levels were determined using real-time polymerase chain reaction.CD4 + CD25 + Foxp3 + T cells were assessed using flow cytometry.Results: Symptom scores, serum Derf-specific IgE levels, GATA-3 mRNA levels, IL-13 mRNA levels, and tissue eosinophil counts decreased in both the S and C groups (P<0.05).Additionally, the percentage of CD4 + CD25 + Foxp3 + T cells, IL-10 levels, and Foxp3 mRNA levels increased in the S and C groups compared with those in the Derf group (P<0.05).AEBSF treatment decreased the proteolytic activity in the S and C groups (P<0.05).Conclusions: Prophylactic and therapeutic treatment with AEBSF significantly reduces allergic airway inflammation and can induce regulatory T cells in a murine model of AR.