Prostaglandin E2 suppresses staphylococcal enterotoxin-induced eosinophilia-associated cellular responses dominantly through an E-prostanoid 2-mediated pathway in nasal polyps

Mitsuhiro Okano, Tazuko Fujiwara, Takenori Haruna, Shin Kariya, Seiichiro Makihara, Takaya Higaki, Kazunori Nishizaki

Research output: Contribution to journalArticle

30 Citations (Scopus)

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) E2, 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 PGE2 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. PGE2 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 PGE2 inhibits the pathogenesis of SEB-induced eosinophilic inflammation primarily through the EP2-mediated pathway in patients with chronic rhinosinusitis with nasal polyposis.

Original languageEnglish
Pages (from-to)868-874.e13
JournalJournal of Allergy and Clinical Immunology
Volume123
Issue number4
DOIs
Publication statusPublished - Apr 2009

Keywords

  • COX
  • E-prostanoid receptor
  • Enterotoxin
  • IL-13
  • IL-5
  • RANTES
  • chronic rhinosinusitis
  • nasal polyps
  • prostaglandin E

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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