Serine Protease Inhibitor Attenuates Ovalbumin Induced Inflammation in Mouse Model of Allergic Airway Disease

Abstract

BackgroundSerine proteases promote inflammation and tissue remodeling by activating proteinase-activated receptors, urokinase, metalloproteinases and angiotensin. In the present study, 4-(2-Aminoethyl) benzenesulfonyl fluoride (AEBSF) a serine protease inhibitor was evaluated for prophylactic and therapeutic treatment in mouse model of airway allergy.MethodsBALB/c mice were sensitized by i.p route and challenged with ovalbumin. They were treated i.n. with 2, 10 and 50 µg of AEBSF, one hour before or after challenge and euthanized to collect BALF (bronchoalveolar lavage fluid), blood and lungs. Proteolytic activity, total cell/eosinophil/neutrophil count eosinophil peroxidase activity (EPO), IL-4, IL-5, IL-10, IL-13, cysteinyl leukotrienes and 8-isoprostane were determined in BALF and immunoglobulins were measured in serum. H&E and PAS stained lung sections were examined for cellular infiltration and airway inflammation.ResultsMice exposed to ovalbumin and treated with PBS showed increased cellular infiltration in lungs and higher serum IgE, IgG1 and IgG2a levels as compared to sham mice. Treatment with AEBSF reduced total cells/eosinophil/neutrophil infiltration. Both prophylactic and therapeutic AEBSF treatment of 10 or 50 µg reduced serum IgE and IgG1 significantly (p<0.05) than control. AEBSF treatment reduced the proteolytic activity in BALF. IL-4 IL-5 and IL-13 levels decreased significantly (p<0.05) after AEBSF treatment while IL-10 levels increased significantly (p<0.05) in BALF. Airway inflammation and goblet cell hyperplasia reduced as demonstrated by lung histopathology, EPO activity and cysteinyl leukotrienes in BALF after treatment. AEBSF treatment also suppressed oxidative stress in terms of 8-isoprostane in BALF. Among the treatment doses, 10 or 50 µg of AEBSF were most effective in reducing the inflammatory parameters.ConclusionsProphylactic and therapeutic treatment with serine protease inhibitor attenuates the airway inflammation in mouse model of airway allergy and have potential for adjunct therapy.

Anaphylaxis Induced by a Drug Containing Lysozyme and Papain: Influence of Papain on the IgE Response

“…Allergen absorption from the human mucosa has been demonstrated [23] and it would be worth investigating if it could be intensified in the presence of proteases. Actually, targeting proteolytic activity by inhibitors has shown potential for adjunct airway allergy therapy [24]. …”

A Brief Exposure to Tryptase or Thrombin Potentiates Fibrocyte Differentiation in the Presence of Serum or Serum Amyloid P

“…This receptor is found on a variety of cells including monocytes (33), and mediates the ability of tryptase to increase the proliferation of, and collagen production by, fibroblasts (37). Intratracheal administration of tryptase causes inflammation, and inhibition of tryptase attenuates this inflammation (43–46). Inhibition of PAR-2 receptors attenuates collagen deposition in a heart disease model (47).…”

The Effect of Serine Protease Inhibitors on Airway Inflammation in a Chronic Allergen-Induced Asthma Mouse Model

“…The chronic inflammation in asthma is characterized by eosinophilic recruitment, airway hyperresponsiveness (AHR), goblet cell hyperplasia/metaplasia, epithelial hypertrophy/hyperplasia, mucus hypersecretion, collagen deposition, smooth muscle cell hypertrophy/hyperplasia, and subepithelial fibrosis [1, 2]. …”