M. Yamashita et al., DUAL EFFECTS OF AURANOFIN ON PROSTAGLANDIN E-2 PRODUCTION BY RAT PERITONEAL-MACROPHAGES, European journal of pharmacology, 325(2-3), 1997, pp. 221-227
Incubation of rat peritoneal macrophages in medium containing various
concentrations of auranofin (1, 3 and 10 mu M) increased prostaglandin
E-2 production at 4 h in a concentration-dependent manner, in accorda
nce with the increase in the release of [H-3]arachidonic acid from mem
brane phospholipids. However, at 20 h, no stimulation of prostaglandin
E-2 production by auranofin was observed. When the peritoneal macroph
ages were incubated in the presence of 12-O-tetradecanaylphorbol 13-ac
etate (TPA), thapsigargin or A23187, prostaglandin E-2 production at 4
and 20 h was enhanced. The stimulator-induced prostaglandin E-2 produ
ction at 20 h was suppressed by 10 mu M of auranofin. Western blot ana
lysis demonstrated that auranofin inhibited the induction of cyclooxyg
enase 2 by TPA, thapsigargin or A23187 at 4 and 20 h. The level of cyc
looxygenase 1 did not change by treatment with these stimulators in th
e presence or absence of auranofin. These findings suggest that aurano
fin has dual effects on prostaglandin E-2 production: without stimulat
ion, auranofin increases prostaglandin E-2 production at 4 h due to th
e increased release of arachidonic acid which is converted to prostagl
andin E-2 mainly by cyclooxygenase 1, but inhibits the stimulator-indu
ced late-phase prostaglandin E-2 production by inhibiting the inductio
n of cyclooxygenase 2. (C) 1997 Elsevier Science B.V.