Background: Cyclooxygenase (COX)-2 activity has been said to have a protective effect in asthmatic patients as a result of prostaglandin E2 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 μg 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 100 mg/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. © 2007 SEPAR.
|Journal||Archivos de Bronconeumologia|
|Publication status||Published - 1 Jan 2009|
- Mast cell
- Ovalbumin-sensitized mouse
Torres, R., Pérez, M., Marco, A., Picado, C., & de Mora, F. (2009). A Cyclooxygenase-2 Selective Inhibitor Worsens Respiratory Function and Enhances Mast Cell Activity in Ovalbumin-Sensitized Mice. Archivos de Bronconeumologia, 45(4), 162-167. https://doi.org/10.1016/S1579-2129(09)71015-8