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

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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
JournalJournal of Allergy and Clinical Immunology
Volume123
Issue number4
DOIs
Publication statusPublished - Apr 2009

Fingerprint

Nasal Polyps
Enterotoxins
Eosinophilia
Dinoprostone
Prostaglandins
Diclofenac
Interleukin-5
Chemokine CCL5
Interleukin-13
Nose
Cytokines
Indomethacin
Digestion
Cultured Cells
Inflammation
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

@article{8c8c03621da64989ae39860ec0b50c50,
title = "Prostaglandin E2 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) 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.",
keywords = "chronic rhinosinusitis, COX, E-prostanoid receptor, Enterotoxin, IL-13, IL-5, nasal polyps, prostaglandin E, RANTES",
author = "Mitsuhiro Okano and Tazuko Fujiwara and Takenori Haruna and Shin Kariya and Seiichiro Makihara and Takaya Higaki and Kazunori Nishizaki",
year = "2009",
month = "4",
doi = "10.1016/j.jaci.2009.01.047",
language = "English",
volume = "123",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "4",

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TY - JOUR

T1 - Prostaglandin E2 suppresses staphylococcal enterotoxin-induced eosinophilia-associated cellular responses dominantly through an E-prostanoid 2-mediated pathway in nasal polyps

AU - Okano, Mitsuhiro

AU - Fujiwara, Tazuko

AU - Haruna, Takenori

AU - Kariya, Shin

AU - Makihara, Seiichiro

AU - Higaki, Takaya

AU - Nishizaki, Kazunori

PY - 2009/4

Y1 - 2009/4

N2 - 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.

AB - 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.

KW - chronic rhinosinusitis

KW - COX

KW - E-prostanoid receptor

KW - Enterotoxin

KW - IL-13

KW - IL-5

KW - nasal polyps

KW - prostaglandin E

KW - RANTES

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U2 - 10.1016/j.jaci.2009.01.047

DO - 10.1016/j.jaci.2009.01.047

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