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COX / PGE 2 axis critically regulates effects of LPS on eosinophilia‐associated cytokine production in nasal polyps
Author(s) -
Higaki T.,
Okano M.,
Fujiwara T.,
Makihara S.,
Kariya S.,
Noda Y.,
Haruna T.,
Nishizaki K.
Publication year - 2012
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2012.04015.x
Subject(s) - lipopolysaccharide , cytokine , eosinophilia , diclofenac , nasal polyps , immunology , inflammation , enterotoxin , stimulation , interleukin , medicine , chemistry , pharmacology , biochemistry , escherichia coli , gene
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 ( DNPC s). Methods Either diclofenac‐treated or untreated DNPC s 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 DNPC s 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 DNPC s. 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 DNPC s 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 DNPC s, 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 DNPC s, while the addition of EP 2 and EP 4 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.