Role of cyclooxygenase-2, but not cyclooxygenase-1, on type II collagen-induced arthritis in DBA/1J mice

• Published in: Biochemical pharmacology 2003-09, Vol.66 (6), p.1055-1060
• Main Authors: Ochi, Takehiro, Ohkubo, Yoshitaka, Mutoh, Seitaro
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammation; Anti-Inflammatory Agents - therapeutic use; Arachidonic Acid - metabolism; Arthritis, Experimental - drug therapy; Arthritis, Experimental - enzymology; Biological and medical sciences; Collagen Type II; Cyclooxygenase 1; Cyclooxygenase 2; Disease Models, Animal; Edema - etiology; FR140423; Isoenzymes - physiology; Male; Medical sciences; Membrane Proteins; Mice; Mice, Inbred DBA; Pharmacology. Drug treatments; Prostaglandin formation; Prostaglandin-Endoperoxide Synthases - physiology; Prostaglandins - metabolism; Type II collagen arthritis
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(03)00420-9

The purpose of this paper is to explore the contribution of isoforms of cyclooxygenase (COX) to chronic inflammation in DBA/1J mice with type II collagen-induced arthritis (CIA). To address this question pharmacologically, we tested the effects of selective inhibitors of COX-1 and COX-2 on paw edema and the formation of arachidonic acid metabolites in the inflamed paws immunized with type II collagen (CII). Oral administration of FR140423 (3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole), a selective inhibitor of COX-2, showed a dose-dependent anti-inflammatory effect in mouse CIA with ed 50 value of 0.20 mg/kg. Indomethacin, a non-selective inhibitor of COX, also inhibited paw edema in this arthritic model. In contrast, the selective COX-1 inhibitors, FR122047 (1-[(4,5-bis(4-methoxyphenyl)-2-thiazoyl)carbonyl]-4-methylpiperazine hydrochloride) and SC-560 (5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole), had no effect in mouse CIA model. The increase of prostaglandin (PG) E 2 and thromboxane (TX) B 2 in the mouse inflamed paws was associated with the development of paw edema induced by CII. FR140423 dose dependently inhibited the levels of PGE 2 and TXB 2 in the CIA mouse paws with ed 50 values of 0.20 and 0.12 mg/kg, respectively, similar to indomethacin. In contrast, FR122047 and SC-560 had no effect. These results suggest that COX-2, but not COX-1, contributes to the edema and the formation of PGE 2 and TXB 2 in mouse CIA model.