title: Cockroach protease allergen induces allergic airway inflammation via epithelial cell activation.
abstract: Protease allergens are known to enhance allergic inflammation but their exact role in initiation of allergic reactions at mucosal surfaces still remains elusive. This study was aimed at deciphering the role of serine protease activity of Per a 10, a major cockroach allergen in initiation of allergic inflammation at mucosal surfaces. We demonstrate that Per a 10 increases epithelial permeability by disruption of tight junction proteins, ZO-1 and occludin, and enhances the migration of Monocyte derived dendritic cell precursors towards epithelial layer as exhibited by trans-well studies. Per a 10 exposure also leads to secretion of IL-33, TSLP and intracellular Ca2+dependent increase in ATP levels. Further, in vivo experiments revealed that Per a 10 administration in mice elevated allergic inflammatory parameters along with high levels of IL-33, TSLP, IL-1α and uric acid in the mice lungs. We next demonstrated that Per a 10 cleaves CD23 (low affinity IgE receptor) from the surface of PBMCs and purified B cells and CD25 (IL-2 receptor) from the surface of PBMCs and purified T cells in an activity dependent manner, which might favour Th2 responses. In conclusion, protease activity of Per a 10 plays a significant role in initiation of allergic airway inflammation at the mucosal surfaces.
authors.affiliation: Allergy and Immunology Section, CSIR-Institute of Genomics and Integrative Biology, Delhi University Campus, Mall road, Delhi-110007, India.
authors.forename: Sagar L
authors.initials: SL
authors.lastname: Kale
authors.affiliation: Allergy and Immunology Section, CSIR-Institute of Genomics and Integrative Biology, Delhi University Campus, Mall road, Delhi-110007, India.
authors.forename: Komal
authors.initials: K
authors.lastname: Agrawal
authors.affiliation: Department of Respiratory Medicine, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
authors.forename: Shailendra Nath
authors.initials: SN
authors.lastname: Gaur
authors.affiliation: Allergy and Immunology Section, CSIR-Institute of Genomics and Integrative Biology, Delhi University Campus, Mall road, Delhi-110007, India.
authors.forename: Naveen
authors.initials: N
authors.lastname: Arora
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002463:Cell Membrane Permeability; D002465:Cell Movement; D003058:Cockroaches / Q000201:enzymology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000473:pathology*; D000067596:Interleukin-33 / Q000378:metabolism; D008168:Lung / Q000473:pathology*; D008807:Mice, Inbred BALB C; D010447:Peptide Hydrolases / Q000378:metabolism*; D013997:Time Factors; D014527:Uric Acid / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000485:Allergens; D015703:Antigens, CD; D016207:Cytokines; D000067596:Interleukin-33; D014527:Uric Acid; D010447:Peptide Hydrolases; D000094632:Thymic Stromal Lymphopoietin