Role of prostaglandin H synthase-2 in prostaglandin E2 formation in rat carrageenin-induced pleurisy.
Rat carrageenin-induced pleurisy was used to clarify the role of prostaglandin H synthase (PGHS)-2 in acute inflammation. Intrapleural injection of 0.2 ml of 2% lambda-carrageenin induced accumulation of exudate and infiltration of leukocytes into the pleural cavity. When PGHS-1 and -2 proteins in the pleural exudate cells were analyzed by Western blot analysis, PGHS-2 was detectable from 1 hr after carrageenin injection. Its level rose sharply, remained high from 3 to 7 hr after injection, and then fell to near the detection limit. PGHS-1 was also detected, but kept almost the same level throughout the course of the pleurisy. Levels of prostaglandin (PG) E2 and thromboxane (TX) B2 in the exudate increased from hour 3 to hour 7, and then declined. Thus, the changes of the level of PGE2 were closely paralleled those of PGHS-2. The selective PGHS-2 inhibitors NS-398, nimesulide and SC-58125 suppressed the inflammatory reaction and caused a marked decrease in the level of PGE2 but not in those of TXB2 and 6-keto-PGF 1 alpha. These results suggest that the PGHS-2 expressed in the pleural exudate cells may be involved in PGE2 formation at the site of inflammation.
Harada
Y
Y
Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Japan.
Hatanaka
K
K
Kawamura
M
M
Saito
M
M
Ogino
M
M
Majima
M
M
Ohno
T
T
Ogino
K
K
Yamamoto
K
K
Taketani
Y
Y
Yamamoto
S
S
Katori
M
M
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001391:Azo Compounds / Q000378:metabolism; D015153:Blotting, Western; D002351:Carrageenan / Q000494:pharmacology; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D005079:Excipients / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D010994:Pleura / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism; D014343:Trypan Blue
D000893:Anti-Inflammatory Agents; D001391:Azo Compounds; D004396:Coloring Agents; D016861:Cyclooxygenase Inhibitors; D005079:Excipients; D007527:Isoenzymes; D009578:Nitrobenzenes; D011720:Pyrazoles; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C090859:1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole; C009000:pontamine sky blue; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003907:Dexamethasone; D002351:Carrageenan; D011451:Prostaglandin-Endoperoxide Synthases; D014343:Trypan Blue; D015232:Dinoprostone; C012655:nimesulide