Cyclooxygenase-2 expression during allergic inflammation in guinea-pig lungs.
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 D(2) and prostaglandin E(2) spontaneously or in response to A23187 (10 microM) 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.
Oguma
Tsuyoshi
T
Cardiopulmonary Division, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan.
Asano
Koichiro
K
Shiomi
Tetsuya
T
Fukunaga
Kouichi
K
Suzuki
Yusuke
Y
Nakamura
Morio
M
Matsubara
Hiroaki
H
Sheldon
Holly K
HK
Haley
Kathleen J
KJ
Lilly
Craig M
CM
Drazen
Jeffrey M
JM
Yamaguchi
Kazuhiro
K
D000818:Animals; D051546:Cyclooxygenase 2; D006168:Guinea Pigs; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D010544:Peroxidases / Q000096:biosynthesis*; D011014:Pneumonia / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012130:Respiratory Hypersensitivity / Q000201:enzymology*
D007527:Isoenzymes; D010544:Peroxidases; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases