Role of prostaglandin H synthase-2 in prostaglandin E(2) 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) E(2) and thromboxane (TX) B-2 in the exudate increased from hour 3 to hour 7, and then declined. Thus, the changes of the level of PGE(2) 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 PGE(2) but not in those of TXB(2) and 6-keto-PGF(1 alpha). These results suggest that the PGHS-2 expressed in the pleural exudate cells may be involved in PGE(2) formation at the site of inflammation.