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ID 49563
FullText URL
Author
Higaki, T
Fujiwara, T
Makihara, S
Noda, Y
Haruna, T
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