title: The effect of calprotectin on TSLP and IL-25 production from airway epithelial cells.
abstract: BACKGROUND
  Calprotectin is a heterodimer complex of the S100A8 and S100A9 proteins, and has various functions as an innate mediator at the sites of inflammation. The aim of this study was to elucidate the roles of calprotectin in the eosinophilic chronic rhinosinusitis (ECRS).
  
  
  METHODS
  Allergen-induced production of calprotectin was evaluated in cultured normal human bronchial epithelial (NHBE) cells by ELISA and RT-PCR. We then examined the roles of calprotectin on Alternaria alternata (Alternaria)-induced production of thymic stromal lymphopoietin (TSLP) and IL-25 in NHBE cells. The extracellular concentration and allergen-induced secretion of calprotectin in cultured primary nasal epithelial (PNE) cells were examined and compared between patients with ECRS and non-eosinophilic chronic rhinosinusitis (NECRS).
  
  
  RESULTS
  Alternaria, house dust mites, protease from Staphylococcus aureus, papain, trypsin, polyinosinic:polycytidylic acid and lipopolysaccharide stimulated calprotectin production in the cultured NHBE cells. The combination of calprotectin and ATP stimulated the production of TSLP and IL-25 in NHBE cells, and calprotectin stimulated Alternaria-induced production of TSLP and IL-25, which was suppressed by blocking P2 purinergic receptors and by treatment with siRNA for S100A8, S100A9 or calprotectin receptors (Toll-like receptor 4 or receptor for advanced glycation end products). Allergen-induced calprotectin production was significantly stimulated in PNE cells from patients with ECRS.
  
  
  CONCLUSIONS
  These results indicate that calprotectin enhances the allergen-induced Th2-type inflammatory responses in airway epithelial cells via the secretion of TSLP and IL-25, and that calprotectin secreted by the epithelial cells may be involved in the pathogenesis of ECRS.
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Japan. Electronic address: tomohi@belle.shiga-med.ac.jp.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Kato
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: Shiseido Research Center, Yokohama, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hosoi
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology; D000818:Animals; D015415:Biomarkers; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004802:Eosinophilia / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D039841:Leukocyte L1 Antigen Complex / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism*; D012220:Rhinitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012852:Sinusitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism; D055815:Young Adult; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000485:Allergens; D015415:Biomarkers; D016207:Cytokines; C486701:IL25 protein, human; D020381:Interleukin-17; D039841:Leukocyte L1 Antigen Complex; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D000255:Adenosine Triphosphate; D000094632:Thymic Stromal Lymphopoietin
keywords: Calprotectin; Eosinophilic chronic rhinosinusitis; IL-25; TSLP; Th2-type inflammation