title: Epithelial Cell-Derived Cytokines Contribute to the Pathophysiology of Eosinophilic Chronic Rhinosinusitis.
abstract: The epithelial cell-derived cytokines, thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33 induce T helper 2 type immune responses. In the present study, we investigate the role of these cytokines in the pathophysiology of eosinophilic chronic rhinosinusitis (ECRS). Nasal tissue specimens from chronic rhinosinusitis patients were assayed for the expression of TSLP, IL-25, IL-33, protease-activated receptor (PAR)-2, and P2Y2 receptor (P2Y2R). Cytokine production in cultured nasal epithelial cells (PNECs) was also examined. The mRNA levels of TSLP and IL-25 and the concentrations of IL-25 and IL-33 increased in PNECs from ECRS patients. Immunohistological staining demonstrated that TSLP, IL-25, and IL-33 were localized in the epithelial cells of nasal polyps, and that their expression was increased in ECRS. The mRNA levels of TSLP and IL-25 correlated with the clinical severity of ECRS, as indicated by the computed tomography score. The TSLP mRNA levels and IL-33 protein concentration correlated with the number of eosinophils in the nasal polyps of patients with ECRS. Airborne allergen-induced cytokine production increased in PNECs of these patients. Expression levels of the PAR-2 and P2Y2R increased in cultured PNECs and nasal polyps from patients with ECRS. The results indicate that increased induction and expression of TSLP, IL-25, and IL-33 from nasal epithelial cells contribute to the pathophysiology of ECRS.
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science , Otsu, Japan .
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kouzaki
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science , Otsu, Japan .
authors.forename: Koji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science , Otsu, Japan .
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science , Otsu, Japan .
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tojima
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science , Otsu, Japan .
authors.forename: Shino
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science , Otsu, Japan .
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics* / Q000276:immunology; D000067596:Interleukin-33 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology / Q000601:surgery; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D044464:Receptor, PAR-2 / Q000235:genetics / Q000276:immunology; D058473:Receptors, Purinergic P2Y2 / Q000235:genetics / Q000276:immunology; D012220:Rhinitis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology / Q000601:surgery; D012720:Severity of Illness Index; D015398:Signal Transduction; D012852:Sinusitis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology / Q000601:surgery; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; C486701:IL25 protein, human; C506536:IL33 protein, human; D020381:Interleukin-17; D000067596:Interleukin-33; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D058473:Receptors, Purinergic P2Y2; D000094632:Thymic Stromal Lymphopoietin