Abstract
Epithelial cells at mucosal surfaces are integral components of innate and adaptive immunity. IL-25 is reportedly produced by epithelial cells and likely plays vital roles in regulating type-2 immune responses. However, little is known regarding the mechanisms that control production and extracellular releases of IL-25. We hypothesized that proteases from the multiple allergens may induce IL-25 production in airway epithelial cells. In this study,wefound that IL-25 is constitutively produced and detectable in cytoplasm of resting normal human bronchial epithelial (NHBE) cells. When exposed to airborne allergens such as house dust mite (HDM), stored IL-25 was released rapidly to the extracellular space. IL-25 release was not accompanied by cell death, suggesting involvement of active secretory mechanism(s). HDM also enhanced IL-25 mRNA transcription, which was dependent on their protease activities. Furthermore, activation of NHBE cells with authentic proteases, such as trypsin and papain, or with a peptide agonist for protease-activated receptor 2 was sufficient to enhance IL-25 mRNA transcription and protein. Protease-driven increase in mRNA transcription and allergen-driven extracellular release of IL-25 protein was also observed in primary nasal epithelial cells from healthy individuals. These findings suggest that IL-25 production by airway epithelial cells is regulated by the transcription and protein release levels and that allergen proteases likely play pivotal roles in both biological processes.
Original language | English (US) |
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Pages (from-to) | 741-750 |
Number of pages | 10 |
Journal | American journal of respiratory cell and molecular biology |
Volume | 49 |
Issue number | 5 |
DOIs | |
State | Published - Nov 2013 |
Keywords
- Airway epithelial cells
- Allergen
- IL-25
- PAR-2
- Protease
ASJC Scopus subject areas
- Molecular Biology
- Pulmonary and Respiratory Medicine
- Clinical Biochemistry
- Cell Biology