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

Abstract.

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 (1-100mg/kg) and indomethacin (0.03-10mg/kg) were administered orally. JTE-522 and reference compounds (0.01-10 μM) 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 10mg/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 gastrointestinal tract.