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Proteolytic activity of both allergens and intrinsic cellular proteases are important mediators of allergic pathophysiology including epithelial barrier permeability, cytokine production, and immune cell recruitment, among others. Ongoing studies are focused on the highly homologous serine protease inhibitors SERPINB3 and SERPINB4 in asthma and atopic dermatitis. Preliminary studies have demonstrated that the mouse homolog of these SERPINs contribute to asthma pathophysiology. Current research focuses on elucidating the mechanism by which these proteases mediate their function in the lung, and evaluating their contribution to atopic dermatitis, a skin allergic disease.
Reprinted from J Allergy Clin Immunol, Jan 2011, Decreased FOXA3 expression in Serpinb3a-null (KO) mice after HDM challenge. A, FOXA3 staining in WT and Serpinb3a-null mice after PBS or HDM challenge. A representative image at ×200 magnification from each treatment is shown. B, Quantitation of FoxA3 staining. Black bar, WT+HDM; white bar, KO+HDM. P values are shown only for statistically significant differences. n = 13 for WT+HDM and KO+HDM. Vol 127, Iss 1, pgs. 254-256 e6, Copyright@ 2014 with permission from Elsevier.
SERPINB3 and SERPINB4 are induced in response to IL-13, a key regulator of clearance of nematode infections. A second project is currently examining the role of these SERPINs in intestinal inflammation.
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