Transcription of Interleukin-25 and extracellular release of the protein is regulated by allergen proteases in airway epithelial cells

Hideaki Kouzaki, Ichiro Tojima, Hirohito Kita, Takeshi Shimizu

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


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 languageEnglish (US)
Pages (from-to)741-750
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Issue number5
StatePublished - Nov 2013


  • Airway epithelial cells
  • Allergen
  • IL-25
  • PAR-2
  • Protease

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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