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

Objective and Design: To investigate the effect of JTE-522, a selective cyc looxygenase (COX)-2 inhibitor, on prostaglandin (PG) production and COX exp ression in rats. Subjects: Male rats (4-8 weeks old) were used for in vivo experiments, whil e for in vitro assay, rat peritoneal macrophages were used. Treatment: JTE-522 (1-100 mg/kg) and indomethacin (0.03-10 mg/kg) were admi nistered orally. JTE-522 and reference compounds (0.01-10 mu M) were subjec ted to COX expression. Results: JTE-522 inhibited the development of carrageenin-induced paw edema and PGE(2) production in inflammatory paws at a dose of 10 mg/kg. On the o ther hand, JTE-522 (1-100 mg/kg) did not affect A23187-stimulated thromboxa ne B-2 release from whole blood or the PGE(2) level in gastric mucosa. JTE- 522 did not suppress lipopolysaccharide-induced COX-2 expression in periton eal macrophages. Conclusion: These results indicate that JTE-522 selectively inhibits PG pro duction mediated by COX-2 in inflammatory tissues. JTE-522 may thus represe nt a novel type of antiinflammatory drug without adverse effects on the gas trointestinal tract.