title: Transcription of interleukin-25 and extracellular release of the protein is regulated by allergen proteases in airway epithelial cells.
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, we found 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.
authors.affiliation: 1 Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Shiga, Japan; and.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kouzaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tojima
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000485:Allergens / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology* / Q000378:metabolism; D060829:Arthropod Proteins / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D004847:Epithelial Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000276:immunology* / Q000378:metabolism; D039981:Pyroglyphidae / Q000201:enzymology / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism; D020545:Respiratory Mucosa / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D051193:Toll-Like Receptors / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C486701:IL25 protein, human; D020381:Interleukin-17; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D051193:Toll-Like Receptors; D010447:Peptide Hydrolases