Cockroach protease allergen induces allergic airway inflammation via epithelial cell activation

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...

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Bibliographic Details
Published in:Scientific reports 2017-02, Vol.7 (1), p.42341-42341, Article 42341
Main Authors: Kale, Sagar L., Agrawal, Komal, Gaur, Shailendra Nath, Arora, Naveen
Format: Article
Language:English
Subjects:
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Allergens
Allergies
Calcium (intracellular)
CD23 antigen
CD25 antigen
Cell activation
Dendritic cells
Humanities and Social Sciences
Hypersensitivity
Immunoglobulin E
Inflammation
Interleukin 2
Interleukin 2 receptors
Leukocyte migration
Lymphocytes B
Lymphocytes T
Membrane permeability
Monocytes
Mucosa
multidisciplinary
Proteases
Respiratory tract
Respiratory tract diseases
Science
Serine
Serine proteinase
Thymic stromal lymphopoietin
Uric acid
Zonula occludens-1 protein
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Summary: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 Ca 2+ 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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep42341