Augmentation of allergic inflammation in the airways of cyclooxygenase-2-deficient mice.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These data indicate that COX-2 deficiency augments allergic inflammation and mucous cell metaplasia.
Nakata
Junko
J
First Department of Medicine, Tokyo Women's Medical University School of Medicine, Shinjuku, Tokyo.
Kondo
Mitsuko
M
Tamaoki
Jun
J
Takemiya
Takako
T
Nohara
Michiko
M
Yamagata
Kanato
K
Nagai
Atsushi
A
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000172:deficiency* / Q000235:genetics; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003545:Cysteine / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D018793:Interleukin-13 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008679:Metaplasia; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D013449:Sulfonamides / Q000494:pharmacology
D016085:Bronchoconstrictor Agents; D016861:Cyclooxygenase Inhibitors; D018793:Interleukin-13; D015289:Leukotrienes; D013449:Sulfonamides; C112381:cysteinyl-leukotriene; D016210:Methacholine Chloride; D016718:Arachidonic Acid; D007073:Immunoglobulin E; D010047:Ovalbumin; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D003545:Cysteine; C012655:nimesulide