title: Cellular responses to Staphylococcus aureus alpha-toxin in chronic rhinosinusitis with nasal polyps.
abstract: BACKGROUND
  In contrast to Staphylococcus aureus-derived superantigenic exotoxins, the role of non-superantigenic exotoxins in the pathogenesis of eosinophilic airway diseases remains obscure. We sought to characterize S. aureus alpha-toxin-induced cellular responses in chronic rhinosinusitis with nasal polyps (CRSwNP).
  
  
  METHODS
  Dispersed nasal polyp cells and uncinate tissue cells were prepared from patients with CRS with and without nasal polyps, respectively. Cells were incubated with various concentrations of alpha-toxin or staphylococcal enterotoxin B and then the levels of IL-5, IL-13, IFN-γ, IL-17A, and IL-10 in the cell supernatants were determined. The pathophysiological significance of alpha-toxin-induced cytokine production was also determined including radiological severity of rhinosinusitis, tissue and blood eosinophilia, serum total IgE level, and 1-s forced expiratory volume/forced vital capacity ratio (FEV1/FVC).
  
  
  RESULTS
  Nasal polyp cells produced substantial amounts of IL-5, IL-13, IFN-γ, IL-17A, and IL-10 in response to alpha-toxin. Cytokine production was higher in nasal polyp cells than in uncinate tissue cells. The potency of alpha-toxin in stimulating IL-5, IL-13, and IL-10 production was comparable to that of enterotoxin. Alpha-toxin-induced IFN-γ, IL-17A, and IL-10 production significantly and negatively correlated with the degree of eosinophil infiltration into nasal polyps. Conversely, alpha-toxin-induced IFN-γ and IL-10 production significantly and positively correlated with FEV1/FVC. IL-10 production was significantly lower in asthmatic patients compared to non-asthmatics
  
  
  CONCLUSIONS
  S. aureus-derived alpha-toxin can provoke cellular responses in nasal polyps. These responses, especially failure to synthesize IL-10, may play a role in the pathophysiology of CRSwNP.
authors: Department of Otolaryngology-Head & Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Mitsuhiro
authors: M
authors: Okano
authors: Department of Otolaryngology-Head & Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Tazuko
authors: T
authors: Fujiwara
authors: Department of Otolaryngology-Head & Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Shin
authors: S
authors: Kariya
authors: Department of Otolaryngology-Head & Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Takaya
authors: T
authors: Higaki
authors: Department of Otolaryngology-Head & Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Takenori
authors: T
authors: Haruna
authors: Department of Microbiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Osamu
authors: O
authors: Matsushita
authors: Department of Otolaryngology-Head & Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Yohei
authors: Y
authors: Noda
authors: Department of Otorhinolaryngology, Kagawa Rosai Hospital, Kagawa, Japan.
authors: Seiichiro
authors: S
authors: Makihara
authors: Department of Otorhinolaryngology, Kagawa Prefectural Central Hospital, Kagawa, Japan.
authors: Kengo
authors: K
authors: Kanai
authors: Department of Otolaryngology-Head & Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Yasuyuki
authors: Y
authors: Noyama
authors: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Kanagawa, Japan.
authors: Masami
authors: M
authors: Taniguchi
authors: Department of Otolaryngology-Head & Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Kazunori
authors: K
authors: Nishizaki
mesh_terms: D000328:Adult; D000368:Aged; D001427:Bacterial Toxins / Q000276:immunology*; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006460:Hemolysin Proteins / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000150:complications* / Q000378:metabolism; D012220:Rhinitis / Q000150:complications* / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D012852:Sinusitis / Q000150:complications* / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D001427:Bacterial Toxins; D016207:Cytokines; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin; D007073:Immunoglobulin E