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ID 49563
FullText URL
Author
Higaki, T
Okano, M
Fujiwara, T
Makihara, S
Noda, Y
Haruna, T
Nishizaki, K Kaken ID researchmap
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-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.
Keywords
COX
cytokine
LPS
PGE(2)
Staphylococcal enterotoxin B
Published Date
2012-08
Publication Title
Clinical and Experimental Allergy
Volume
volume42
Issue
issue8
Start Page
1217
End Page
1226
ISSN
0954-7894
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1111/j.1365-2222.2012.04015.x
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/49123
language
英語
File Version
author
Refereed
True
DOI
Web of Science KeyUT