Protease Inhibitor Reduces Airway Response and Inflammation In Mouse Model Of Cockroach Allergy

Abstract

RationaleSerine protease(s) are potent inducer of airway resistance and inflammation and the allergic response may be modified by proteases inhibitor. In the present study, effect of serine protease inhibitor in cockroach allergen induced airway resistance and inflammation was determined in mouse model.MethodsMice were immunized with cockroach extract (CE) or Per a 10 and treated with 4-(2-Aminoethyl) benzenesulfonyl fluoride (AEBSF) 1 h before challenge. AHR was measured, one day after the last challenge and mice were euthanized to get BALF, blood and lung to evaluate of inflammation and oxidative stress.ResultsAEBSF treatment to mice reduced more than 90% AHR in CE and in Per a 10 challenged mice (p<0.05). EPO, IgE, IL-4, IL-5 and IL-13 levels were significantly (p<0.05) reduced in AEBSF treated mice as compared to untreated group. The treatment lowered the total cell, eosinophil and neutrophil count in BALF to 90, 80 and 83 % in CE and 100, 62 and 90 % in Per a 10 challenged mice (p<0.05), respectively. Lung histology revealed that AEBSF treated mice had reduced inflammation and low mucus production in airways. Furthermore, the treatment had significantly reduced 8-isoprostane and ROS level to 88 and 86 in CE and 82 and 83 % in per a 10 challenged mice in comparison to untreated group (p<0.05).ConclusionsAEBSF reduces allergen induced airway resistance and inflammation indicating that it might be used in “add-on” therapy for respiratory diseases. The therapeutic effect of inhibitor is independent of protease activity of allergen. RationaleSerine protease(s) are potent inducer of airway resistance and inflammation and the allergic response may be modified by proteases inhibitor. In the present study, effect of serine protease inhibitor in cockroach allergen induced airway resistance and inflammation was determined in mouse model. Serine protease(s) are potent inducer of airway resistance and inflammation and the allergic response may be modified by proteases inhibitor. In the present study, effect of serine protease inhibitor in cockroach allergen induced airway resistance and inflammation was determined in mouse model. MethodsMice were immunized with cockroach extract (CE) or Per a 10 and treated with 4-(2-Aminoethyl) benzenesulfonyl fluoride (AEBSF) 1 h before challenge. AHR was measured, one day after the last challenge and mice were euthanized to get BALF, blood and lung to evaluate of inflammation and oxidative stress. Mice were immunized with cockroach extract (CE) or Per a 10 and treated with 4-(2-Aminoethyl) benzenesulfonyl fluoride (AEBSF) 1 h before challenge. AHR was measured, one day after the last challenge and mice were euthanized to get BALF, blood and lung to evaluate of inflammation and oxidative stress. ResultsAEBSF treatment to mice reduced more than 90% AHR in CE and in Per a 10 challenged mice (p<0.05). EPO, IgE, IL-4, IL-5 and IL-13 levels were significantly (p<0.05) reduced in AEBSF treated mice as compared to untreated group. The treatment lowered the total cell, eosinophil and neutrophil count in BALF to 90, 80 and 83 % in CE and 100, 62 and 90 % in Per a 10 challenged mice (p<0.05), respectively. Lung histology revealed that AEBSF treated mice had reduced inflammation and low mucus production in airways. Furthermore, the treatment had significantly reduced 8-isoprostane and ROS level to 88 and 86 in CE and 82 and 83 % in per a 10 challenged mice in comparison to untreated group (p<0.05). AEBSF treatment to mice reduced more than 90% AHR in CE and in Per a 10 challenged mice (p<0.05). EPO, IgE, IL-4, IL-5 and IL-13 levels were significantly (p<0.05) reduced in AEBSF treated mice as compared to untreated group. The treatment lowered the total cell, eosinophil and neutrophil count in BALF to 90, 80 and 83 % in CE and 100, 62 and 90 % in Per a 10 challenged mice (p<0.05), respectively. Lung histology revealed that AEBSF treated mice had reduced inflammation and low mucus production in airways. Furthermore, the treatment had significantly reduced 8-isoprostane and ROS level to 88 and 86 in CE and 82 and 83 % in per a 10 challenged mice in comparison to untreated group (p<0.05). ConclusionsAEBSF reduces allergen induced airway resistance and inflammation indicating that it might be used in “add-on” therapy for respiratory diseases. The therapeutic effect of inhibitor is independent of protease activity of allergen. AEBSF reduces allergen induced airway resistance and inflammation indicating that it might be used in “add-on” therapy for respiratory diseases. The therapeutic effect of inhibitor is independent of protease activity of allergen.