start-ver=1.4
cd-journal=joma
no-vol=42
cd-vols=
no-issue=8
article-no=
start-page=1217
end-page=1226
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=201208
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=COX/PGE(2) axis critically regulates effects of LPS on eosinophilia-associated cytokine production in nasal polyps
en-subtitle=
kn-subtitle=
en-abstract=
kn-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.
en-copyright=
kn-copyright=

en-aut-name=HigakiT
en-aut-sei=Higaki
en-aut-mei=T
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OkanoM
en-aut-sei=Okano
en-aut-mei=M
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=FujiwaraT
en-aut-sei=Fujiwara
en-aut-mei=T
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MakiharaS
en-aut-sei=Makihara
en-aut-mei=S
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KariyaS
en-aut-sei=Kariya
en-aut-mei=S
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NodaY
en-aut-sei=Noda
en-aut-mei=Y
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HarunaT
en-aut-sei=Haruna
en-aut-mei=T
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NishizakiK
en-aut-sei=Nishizaki
en-aut-mei=K
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=
kn-affil=Okayama Univ, Dept Otolaryngol Head & Neck Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=2
en-affil=
kn-affil=Okayama Univ, Dept Otolaryngol Head & Neck Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=3
en-affil=
kn-affil=Okayama Univ, Dept Otolaryngol Head & Neck Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=4
en-affil=
kn-affil=Okayama Univ, Dept Otolaryngol Head & Neck Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=5
en-affil=
kn-affil=Okayama Univ, Dept Otolaryngol Head & Neck Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=6
en-affil=
kn-affil=Okayama Univ, Dept Otolaryngol Head & Neck Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=7
en-affil=
kn-affil=Okayama Univ, Dept Otolaryngol Head & Neck Surg, Grad Sch Med Dent & Pharmaceut Sci

affil-num=8
en-affil=
kn-affil=Okayama Univ, Dept Otolaryngol Head & Neck Surg, Grad Sch Med Dent & Pharmaceut Sci
en-keyword=COX
kn-keyword=COX
en-keyword=cytokine
kn-keyword=cytokine
en-keyword=LPS
kn-keyword=LPS
en-keyword=PGE(2)
kn-keyword=PGE(2)
en-keyword=Staphylococcal enterotoxin B
kn-keyword=Staphylococcal enterotoxin B
END