Role of prostaglandin H synthase-2 in prostaglandin E2 formation in rat carrageenin-induced pleurisy |
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Authors: | Yoshiteru Harada Ko Hatanaka Michiko Kawamura Maki Saito Michiko Ogino Masataka Majima Takashi Ohno Keiko Ogino Kei Yamamoto Yutaka Taketani Shozo Yamamoto Makoto Katori |
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Institution: | aDepartment of Pharmacology, Kitasato University School of Medicine, Sagamihara, 228, Japan;bDepartment of Biochemistry, Tokushima University School of Medicine, Tokushima, 770, Japan;cDepartment of Pharmacology, Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim Co., Ltd., Kawanishi 666-01, Japan |
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Abstract: | 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% λ-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-PGF1α. These results suggest that the PGHS-2 expressed in the pleural exudate cells may be involved in PGE2 formation at the site of inflammation. |
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Keywords: | rat carrageenin-induced pleurisy prostaglandin H synthase-2 NS-398 nimesulide SC-58125 |
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