title: Selective cyclooxygenase-1 and -2 inhibitors each increase allergic inflammation and airway hyperresponsiveness in mice.
abstract: 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.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. Stokes.Peebles@mcmail.vanderbilt.edu
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
authors.forename: Koichi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Jason D
authors.initials: JD
authors.lastname: Morrow
authors.forename: Ryszard
authors.initials: R
authors.lastname: Dworski
authors.forename: Robert D
authors.initials: RD
authors.lastname: Collins
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: John W
authors.initials: JW
authors.lastname: Christman
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Kang
authors.forename: Kasia
authors.initials: K
authors.lastname: Jarzecka
authors.forename: Jamye
authors.initials: J
authors.lastname: Furlong
authors.forename: Daphne B
authors.initials: DB
authors.lastname: Mitchell
authors.forename: Megha
authors.initials: M
authors.lastname: Talati
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: James R
authors.initials: JR
authors.lastname: Sheller
mesh_terms: 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
chemical_list: 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