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

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 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-γ 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-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 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.

• Authors: T Higaki, M Okano, T Fujiwara, S Makihara, S Kariya, Y Noda, T Haruna, K Nishizaki
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 42 Issue 8 Pg. 1217-26 (Aug 2012) ISSN: 1365-2222 [Electronic] England
• PMID: 22805469 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Blackwell Publishing Ltd.

Chemical References

• Cytokines
• Enterotoxins
• Lipopolysaccharides
• Receptors, Prostaglandin E, EP2 Subtype
• Receptors, Prostaglandin E, EP4 Subtype
• enterotoxin B, staphylococcal
• Cyclooxygenase 1
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases
• Dinoprostone

Topics

• Adolescent
• Adult
• Aged
• Cells, Cultured
• Cyclooxygenase 1 (genetics, metabolism)
• Cyclooxygenase 2 (genetics, metabolism)
• Cytokines (biosynthesis, immunology)
• Dinoprostone (metabolism)
• Enterotoxins (immunology)
• Eosinophilia (immunology, metabolism)
• Female
• Gene Expression Regulation (drug effects)
• Humans
• Lipopolysaccharides (immunology, pharmacology)
• Male
• Middle Aged
• Nasal Polyps (immunology, metabolism)
• Prostaglandin-Endoperoxide Synthases (genetics, metabolism)
• Receptors, Prostaglandin E, EP2 Subtype (metabolism)
• Receptors, Prostaglandin E, EP4 Subtype (metabolism)
• Signal Transduction (drug effects)
• Th1 Cells (immunology, metabolism)
• Th17 Cells (immunology, metabolism)
• Th2 Cells (immunology, metabolism)
• Young Adult