Serine proteases promote inflammation and tissue remodeling by activating proteinase-activated receptors, urokinase, metalloproteinases and angiotensin. In the present study, AEBSF (4-(2-Aminoethyl) benzenesulfonyl fluoride) a serine protease inhibitor, was evaluated for prophylactic and therapeutic treatment in mouse model of airway allergy.
Methods:
BALB/c mice were sensitized by i.p route on 0 and 14 day and challenged with OVA (25, 26 and 27 day) by i.n. route. Mice were treated i.n. with AEBSF, one hour before/after challenge and sacrificed on day 29 to collect BALF, blood and lungs. OVA specific immunoglobulins were measured in serum. Proteolytic activity, total cell/eosinophil count, eosinophil peroxidase activity (EPO), IL-4, IL-5, IL-10, cysteinyl leukotrienes and 8-isoprostane (oxidative stress marker) were determined in BALF. Haematoxylin and eosin stained lung sections were examined for cellular infiltration and airway inflammation.
Results:
Mice exposed to OVA and treated with PBS showed significantly high levels of IgE, IgG1 and IgG2a as compared to sham mice. Both prophylactic and symptomatic AEBSF treatment reduced serum IgE and IgG1 significantly (p ≤ 0.05) than control, however there was little increment in IgG2a level. AEBSF could effectively reduce the proteolytic activity in BALF. IL-4 and IL-5 decreased significantly (p ≤ 0.05) after AEBSF treatment while a significant (p ≤ 0.05) increase was observed in IL-10 in BALF. Airway inflammation reduced significantly as revealed by lung histopathology, EPO activity and cysteinyl leukotrienes in BALF after treatment. AEBSF also suppressed oxidative stress in terms of 8-isoprostane in BALF. Among the treatment doses, 10 and 50 µg of AEBSF were most effective in reducing majority of the inflammatory parameters.
Conclusions:
Prophylactic and therapeutic treatment of AEBSF attenuates the airway inflammation in mouse model of airway allergy and have potential for the treatment of inflammatory allergic diseases.