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 0.20mg/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.