MISC

2012年8月

COX/PGE(2) axis critically regulates effects of LPS on eosinophilia-associated cytokine production in nasal polyps

CLINICAL AND EXPERIMENTAL ALLERGY
  • T. Higaki
  • ,
  • M. Okano
  • ,
  • T. Fujiwara
  • ,
  • S. Makihara
  • ,
  • S. Kariya
  • ,
  • Y. Noda
  • ,
  • T. Haruna
  • ,
  • K. Nishizaki

42
8
開始ページ
1217
終了ページ
1226
記述言語
英語
掲載種別
DOI
10.1111/j.1365-2222.2012.04015.x
出版者・発行元
WILEY-BLACKWELL

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-gamma within the supernatant were measured. The effects of PGE(2) on LPS-induced responses by diclofenac-treated DNPCs were also examined. LPS-induced PGE(2) production and mRNA expression of COX-1, COX-2 and microsomal PGE(2) synthase-1 (m-PGES-1) were measured.
Results Staphylococcal enterotoxin B induced IL-5, IL-13, IL-17A and IFN-gamma production by DNPCs. Pre-treatment with LPS prior to SEB stimulation inhibited production of these cytokines. After stimulation with LPS, PGE(2) 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 PGE(2) inhibited IL-5, IL-13 and IFN-gamma production. LPS alone induced IL-5, IL-13 and IFN-gamma production by diclofenac-treated DNPCs, while the addition of EP2 and EP4 receptor-selective agonists, as well as PGE(2) 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/PGE(2) axis. For clinical implications, indiscreet use of non-steroidal anti-inflammatory drugs should be avoided in patients with chronic rhinosinusitis with nasal polyps.

Web of Science ® 被引用回数 : 13

リンク情報
DOI
https://doi.org/10.1111/j.1365-2222.2012.04015.x
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000306402600010&DestApp=WOS_CPL

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