title: Prostaglandin E(2) suppresses staphylococcal enterotoxin-induced eosinophilia-associated cellular responses dominantly through an E-prostanoid 2-mediated pathway in nasal polyps.
abstract: BACKGROUND
  Recent investigations have revealed that staphylococcal enterotoxins (SEs), COX metabolism, or both might participate in the pathogenesis of eosinophilic airway diseases, such as chronic rhinosinusitis with nasal polyposis.
  
  
  OBJECTIVE
  We sought to determine whether COX metabolism, especially prostaglandin (PG) E(2), plays a significant role in SE-induced cellular responses in nasal polyps.
  
  
  METHODS
  Dispersed nasal polyp cells (DNPCs) were prepared from nasal polyps by means of enzymatic digestion. DNPCs were cultured with SEB in the presence or absence of COX inhibitors (diclofenac and indomethacin) for 72 hours; then the levels of IL-5, IL-13, RANTES, and eotaxin in the supernatants were measured. The effect of PGE(2) on SEB-induced responses by diclofenac-treated DNPCs was examined, especially in terms of receptor specificity.
  
  
  RESULTS
  DNPCs produced significant amounts of IL-5, IL-13, and RANTES in response to SEB. COX inhibitors significantly increased the production of these cytokines. The degree of local eosinophilia was significantly and positively correlated with the changes in IL-5 production induced by diclofenac treatment. PGE(2) significantly and dose-dependently inhibited SEB-induced IL-5, IL-13, and RANTES production by diclofenac-treated DNPCs. E-prostanoid (EP) 2 receptor-selective agonist strongly inhibited the production of all 3 cytokines. EP3 and EP4 receptor-selective agonists partially suppressed these responses, whereas EP1 receptor-selective agonist did not. Interestingly, all of the combined treatments with 2 of the 4 EP receptor-selective agonists significantly inhibited the SEB-induced responses by diclofenac-treated DNPCs.
  
  
  CONCLUSIONS
  These results suggest that PGE(2) inhibits the pathogenesis of SEB-induced eosinophilic inflammation primarily through the EP2-mediated pathway in patients with chronic rhinosinusitis with nasal polyposis.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Okano
authors.forename: Tazuko
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Takenori
authors.initials: T
authors.lastname: Haruna
authors.forename: Shin
authors.initials: S
authors.lastname: Kariya
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Makihara
authors.forename: Takaya
authors.initials: T
authors.lastname: Higaki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nishizaki
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D004008:Diclofenac / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology*; D004768:Enterotoxins / Q000633:toxicity*; D004802:Eosinophilia / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000188:drug therapy / Q000276:immunology*; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000502:physiology*; D058307:Receptors, Prostaglandin E, EP2 Subtype
chemical_list: D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D004768:Enterotoxins; C545644:PTGER2 protein, human; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D004008:Diclofenac; C031818:enterotoxin B, staphylococcal; D015232:Dinoprostone