Am. J. Respir. Crit. Care Med., Volume 165, Number 3, February 2002, 382-386

Cyclooxygenase-2 Expression during Allergic Inflammation in Guinea-Pig Lungs

TSUYOSHI OGUMA, KOICHIRO ASANO, TETSUYA SHIOMI, KOUICHI FUKUNAGA, YUSUKE SUZUKI, MORIO NAKAMURA, HIROAKI MATSUBARA, HOLLY K. SHELDON, KATHLEEN J. HALEY, CRAIG M. LILLY, JEFFREY M. DRAZEN, and KAZUHIRO YAMAGUCHI

Cardiopulmonary Division, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; and Respiratory Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Prostaglandins and thromboxanes are important modulators of airway physiology. The synthesis of these mediators depends on two isoforms of cyclooxygenase (COX), constitutive COX-1 and inducible COX-2. COX-2 expression has been observed in various inflammatory diseases, but not all aspects of the expression and the role of COX-2 in conditions of allergic inflammation such as asthma are clear. In the present study, we examined the 72-h kinetics of the expression of COX-isoform mRNA in ovalbumin-sensitized and -challenged guinea-pig lungs. The sensitized animals showed a robust and transient induction of COX-2 mRNA expression within 1 h after ovalbumin challenge, whereas their COX-1 mRNA levels remained unchanged. Upregulation of the level and activity of COX-2 protein followed the induction of COX-2 mRNA. Lung slices harvested from ovalbumin-challenged animals released more prostaglandin D₂ and prostaglandin E₂ spontaneously or in response to A23187 (10 µM) ex vivo than did those from unchallenged animals. This response was significantly blocked by the COX-2 selective inhibitors, NS-398 and JTE-522. In vivo administration of NS-398 significantly inhibited the accumulation of eosinophils and neutrophils in the lungs. In conclusion, de novo COX-2 expression during allergic inflammation modifies prostanoid synthesis in the lung and airway pathophysiology.

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