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[A cyclooxygenase-2 selective inhibitor worsens respiratory function and enhances mast cell activity in ovalbumin-sensitized mice].

Authors: Torres, R  Perez, M  Marco, A  Picado, C  De Mora, F 
Citation: Torres R, etal., Arch Bronconeumol. 2009 Apr;45(4):162-7. Epub 2009 Apr 1.
Pubmed: (View Article at PubMed) PMID:19342146
DOI: Full-text: DOI:10.1016/j.arbres.2008.04.007

BACKGROUND: Cyclooxygenase (COX)-2 activity has been said to have a protective effect in asthmatic patients as a result of prostaglandin E(2) production. In order to elucidate the mechanisms involved, we evaluated the impact of selective inhibition of COX-2 with rofecoxib during ovalbumin challenge, assessing mast cell activity and airway response in a murine model of asthma. MATERIAL AND METHODS: Mice were sensitized to ovalbumin (10 microg injected intraperitoneally) and further challenged with 0.5% intranasal ovalbumin. Half the sensitized animals were treated orally with rofecoxib (15 mg/kg/d during the challenge phase). Lung function was measured by whole body plethysmography before and after exposure to ovalbumin. The severity of airway inflammation was evaluated by means of a scoring system. Finally, the serum level of mouse mast cell protease-1 was determined as an indicator of mucosal mast cell activity. RESULTS: Sensitized mice treated with rofecoxib exhibited 2.4-fold greater airway hyperresponsiveness than did vehicle-treated mice at a methacholine concentration of 100mg/ml. A clear trend toward worsening airway inflammation in the presence of rofecoxib was observed, although the difference between rofecoxib-treated and vehicle-treated animals was not significant. These changes were accompanied by a significant increase in mucosal mast cell activity. CONCLUSIONS: Selective pharmacological inhibition of COX-2 during the challenge phase worsens airway function in the ovalbumin -induced murine model of acute asthma. We suggest that this effect might be at least partially explained by the increase in airway mast cell activity.

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CRRD Object Information
CRRD ID: 5135522
Created: 2011-07-26
Species: All species
Last Modified: 2011-07-26
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.