Augmentation of allergic inflammation in the airways of cyclooxygenase‐2‐deficient mice

Abstract

Airway cyclooxygenase-2 (COX-2) is induced by cytokine-mediated inflammation such as occurs in asthma. However, the role of COX-2 in the pathophysiology of asthma is not fully understood. Allergic inflammation, airway responsiveness to methacholine and mucous cell metaplasia after ovalbumin sensitization in the airways of COX-2 deficient (-/-) mice, COX-2 (+/+) mice and C57BL/6J mice treated with a selective COX-2 inhibitor, nimesulide were assessed. Histology, cell analysis, measurements of arachidonic acid metabolites and Th2 cytokine levels in bronchoalveolar lavage fluid (BALF), and measurement of serum IgE were performed. Eosinophil infiltration into the airway wall, and the number of eosinophils in BALF were greater in sensitized COX-2 (-/-) mice than in sensitized COX-2 (+/+) mice. The levels of cysteinyl leukotrienes (LTC4/D4/E4), prostaglandin E2 (PGE2) and interleukin (IL)-13 as well as airway responsiveness did not differ in COX-2 (-/-) mice and COX-2 (+/+) mice. However, sensitized COX-2 (-/-) mice had higher LTC4/D4/E4 and lower PGE2 concentrations compared with non-sensitized COX-2 (-/-) mice. The number of PAS/alcian blue-positive airway epithelial cells and serum IgE were elevated in COX-2 (-/-) mice. Nimesulide-treated mice showed augmented eosinophilic inflammation, LTC4/D4/E4 concentrations and mucous cell metaplasia. These data indicate that COX-2 deficiency augments allergic inflammation and mucous cell metaplasia.