title: IL-22/IL-22R1 signaling regulates the pathophysiology of chronic rhinosinusitis with nasal polyps via alteration of MUC1 expression.
abstract: BACKGROUND
  IL-22 is an IL-10-family cytokine that regulates chronic inflammation. We investigated the role of IL-22 and its receptor, IL-22R1, in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP).
  
  
  METHODS
  IL-22 and IL-22R1 protein and mRNA expression in NP and in uncinate tissues (UT) from CRS and non-CRS patients was examined using immunohistochemistry and real-time PCR, respectively. Dispersed NP and UT cells were cultured with the Staphylococcus aureus exotoxins, staphylococcal enterotoxin B and alpha-toxin, following which exotoxin-induced IL-22 levels and their association with clinicopathological factors were analyzed. Effects of IL-22 on MUC1 expression and cytokine release in NP cells were also determined.
  
  
  RESULTS
  IL-22 and IL-22R1 in NP were mainly expressed in infiltrating inflammatory cells and in epithelial cells, respectively. IL-22 mRNA levels in NP were significantly higher than those in UTs from non-CRS patients whereas IL-22R1 levels were conversely lower in NPs. NP cells produced substantial amounts of IL-22 in response to exotoxins. Exotoxin-induced IL-22 production by NP cells significantly and negatively correlated with the degree of local eosinophilia and postoperative computed tomography (CT) score, whereas conversely it positively correlated with the forced expiratory volume in 1s (FEV1)/forced vital capacity (FVC) ratio. IL-22 significantly enhanced MUC1 mRNA expression in NP cells. IL-22-induced MUC1 mRNA levels were significantly and positively correlated with IL-22R1 mRNA levels in NPs.
  
  
  CONCLUSIONS
  These data suggest that imbalance of IL-22/IL-22R1 signaling regulates the pathogenesis of CRSwNP, including local eosinophilia, via alteration of MUC1 expression.
authors: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Yasuyuki
authors: Y
authors: Noyama
authors: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address: mokano@cc.okayama-u.ac.jp.
authors: Mitsuhiro
authors: M
authors: Okano
authors: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Tazuko
authors: T
authors: Fujiwara
authors: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Shin
authors: S
authors: Kariya
authors: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Takaya
authors: T
authors: Higaki
authors: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Takenori
authors: T
authors: Haruna
authors: Department of Otorhinolaryngology, Kagawa Rosai Hospital, Marugame, Japan.
authors: Sei-Ichiro
authors: SI
authors: Makihara
authors: Department of Otorhinolaryngology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
authors: Kengo
authors: K
authors: Kanai
authors: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Takahisa
authors: T
authors: Koyama
authors: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.
authors: Masami
authors: M
authors: Taniguchi
authors: Ishitoya ENT Clinic, Tokyo, Japan.
authors: Jun-Ichi
authors: JI
authors: Ishitoya
authors: Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, Hirakata, Japan.
authors: Akira
authors: A
authors: Kanda
authors: Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, Hirakata, Japan.
authors: Yoshiki
authors: Y
authors: Kobayashi
authors: Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, Hirakata, Japan.
authors: Mikiya
authors: M
authors: Asako
authors: Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, Hirakata, Japan.
authors: Koichi
authors: K
authors: Tomoda
authors: Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Kazunori
authors: K
authors: Nishizaki
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000096:biosynthesis*; D009298:Nasal Polyps / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D018123:Receptors, Interleukin / Q000378:metabolism*; D012220:Rhinitis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D012852:Sinusitis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D018396:Mucin-1; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C060192:MUC1 protein, human; C415369:interleukin-22 receptor
keywords: Chronic rhinosinusitis with nasal polyps; Exotoxins; IL-22; MUC1; Staphylococcus aureus