Selective cyclooxygenase-1 and -2 inhibitors each increase allergic inflammation and airway hyperresponsiveness in mice.
Nonselective cyclooxygenase (COX) inhibition during allergic sensitization with ovalbumin in a murine model leads to an increase in the Type 2 cytokines interleukin-5 (IL-5) and IL-13; however, the effect of selective COX-1 and COX-2 inhibitors on these cytokines is unknown. We found that COX-1 protein was constitutively expressed in lung tissue. Expression of COX-1 protein did not increase with ovalbumin sensitization, but expression of COX-2 protein did. Ovalbumin-sensitized mice treated with either selective COX-1 inhibitor SC58560 (OVA-COX-1 inhibitor) or selective COX-2 inhibitor SC58236 (OVA-COX-2 inhibitor) had significantly greater airway hyperresponsiveness (p < 0.05) and higher levels of IL-13 (p < 0.05) in lung supernatants than did untreated mice that were ovalbumin sensitized (OVA). Lung mRNA levels for the chemokine receptors CCR1 through CCR5 (expressed on eosinophils, basophils, lymphocytes, and dendritic cells) were increased in the OVA-COX-2 inhibitor and OVA-indomethacin groups. We conclude that in the BALB/c mouse, COX inhibition with either a COX-1 or COX-2 inhibitor during allergen sensitization augments production of IL-13 and increases airway hyperresponsiveness.
Peebles
R Stokes
RS
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. Stokes.Peebles@mcmail.vanderbilt.edu
Hashimoto
Koichi
K
Morrow
Jason D
JD
Dworski
Ryszard
R
Collins
Robert D
RD
Hashimoto
Yuko
Y
Christman
John W
JW
Kang
Kyung-Ho
KH
Jarzecka
Kasia
K
Furlong
Jamye
J
Mitchell
Daphne B
DB
Talati
Megha
M
Graham
Barney S
BS
Sheller
James R
JR
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000032:analysis; D005260:Female; D007114:Immunization; D007378:Interleukins / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008565:Membrane Proteins; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D009930:Organic Chemicals; D010047:Ovalbumin / Q000276:immunology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles; D019707:Receptors, Chemokine / Q000378:metabolism; D013449:Sulfonamides; D000096926:Benzenesulfonamides
D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D007378:Interleukins; D007527:Isoenzymes; D008565:Membrane Proteins; D016210:Methacholine Chloride; D009930:Organic Chemicals; D010047:Ovalbumin; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D019707:Receptors, Chemokine; D013449:Sulfonamides; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C404729:SC 58560; C496512:Ptgs1 protein, mouse