JTE-522 selectively inhibits cyclooxygenase-2-derived prostaglandin production in inflammatory tissues

OBJECTIVE AND DESIGN: To investigate the effect of JTE-522, a selective cyclooxygenase (COX)-2 inhibitor, on prostaglandin (PG) production and COX expression in rats. SUBJECTS: Male rats (4-8 weeks old) were used for in vivo experiments, while for in vitro assay, rat peritoneal macrophages were used. TREATMENT: JTE-522 (1-100 mg/kg) and indomethacin (0.03-10 mg/kg) were administered orally. JTE-522 and reference compounds (0.01-10 microM) were subjected to COX expression. RESULTS: JTE-522 inhibited the development of carrageenin-induced paw edema and PGE2 production in inflammatory paws at a dose of 10 mg/kg. On the other hand, JTE-522 (1-100 mg/kg) did not affect A23187-stimulated thromboxane B2 release from whole blood or the PGE2 level in gastric mucosa. JTE-522 did not suppress lipopolysaccharide-induced COX-2 expression in peritoneal macrophages. CONCLUSION: These results indicate that JTE-522 selectively inhibits PG production mediated by COX-2 in inflammatory tissues. JTE-522 may thus represent a novel type of anti-inflammatory drug without adverse effects on the gastro-intestinal tract.