COX/PGE2 axis critically regulates effects of LPS on eosinophilia-associated cytokine production in nasal polyps

T. Higaki, M. Okano, T. Fujiwara, S. Makihara, S. Kariya, Y. Noda, T. Haruna, K. Nishizaki

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Background: Lipopolysaccharide (LPS) has shown heterogeneous effects on eosinophilic inflammation in airways. However, little is known about how LPS regulates pathogenesis of chronic rhinosinusitis with nasal polyps, a major form of eosinophilic inflammation in the upper airway. Objective: We sought to investigate the effect of LPS on cytokine production by dispersed nasal polyp cells (DNPCs). Methods: Either diclofenac-treated or untreated DNPCs were cultured with or without staphylococcal enterotoxin B (SEB) in the presence or absence of LPS, after which the levels of IL-5, IL-13, IL-17A and IFN-γ within the supernatant were measured. The effects of PGE2 on LPS-induced responses by diclofenac-treated DNPCs were also examined. LPS-induced PGE2 production and mRNA expression of COX-1, COX-2 and microsomal PGE2 synthase-1 (m-PGES-1) were measured. Results: Staphylococcal enterotoxin B induced IL-5, IL-13, IL-17A and IFN-γ production by DNPCs. Pre-treatment with LPS prior to SEB stimulation inhibited production of these cytokines. After stimulation with LPS, PGE2 production and expression of COX-2 and m-PGES-1 mRNA by DNPCs increased significantly. In the presence of diclofenac, the suppressive effects of LPS were eliminated. LPS pre-treatment enhanced SEB-induced IL-5, IL-13 and IL-17A production in diclofenac-treated DNPCs, while addition of PGE2 inhibited IL-5, IL-13 and IFN-γ production. LPS alone induced IL-5, IL-13 and IFN- γ production by diclofenac-treated DNPCs, while the addition of EP2 and EP4 receptor-selective agonists, as well as PGE2 itself, inhibited IL-5 and IL-13 production. Conclusions and Clinical Relevance: These results suggest that the regulatory effects of LPS on eosinophilic airway inflammation are controlled via the COX-2/PGE2 axis. For clinical implications, indiscreet use of non-steroidal anti-inflammatory drugs should be avoided in patients with chronic rhinosinusitis with nasal polyps.

Original languageEnglish
Pages (from-to)1217-1226
Number of pages10
JournalClinical and Experimental Allergy
Volume42
Issue number8
DOIs
Publication statusPublished - Aug 2012

Keywords

  • COX
  • Cytokine
  • LPS
  • PGE
  • Staphylococcal enterotoxin B

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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