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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Arachidonic Acid / metabolism
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Bronchial Hyperreactivity / immunology
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Bronchial Hyperreactivity / metabolism
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Bronchial Hyperreactivity / physiopathology*
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Bronchial Provocation Tests
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Bronchoalveolar Lavage Fluid / chemistry
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Cyclooxygenase 1
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology*
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Dinoprostone / analysis
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Female
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Immunization
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Interleukins / metabolism
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Isoenzymes / antagonists & inhibitors*
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Isoenzymes / metabolism
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Lung / metabolism
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Membrane Proteins
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Methacholine Chloride
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Mice
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Mice, Inbred BALB C
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Organic Chemicals*
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Ovalbumin / immunology
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Prostaglandin-Endoperoxide Synthases / metabolism
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Pyrazoles*
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Receptors, Chemokine / metabolism
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Sulfonamides*
Substances
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4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Interleukins
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Isoenzymes
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Membrane Proteins
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Organic Chemicals
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Pyrazoles
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Receptors, Chemokine
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SC 58560
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Sulfonamides
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Methacholine Chloride
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Arachidonic Acid
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Ovalbumin
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Cyclooxygenase 1
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases
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Ptgs1 protein, mouse
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Dinoprostone