DUAL EFFECTS OF AURANOFIN ON PROSTAGLANDIN E-2 PRODUCTION BY RAT PERITONEAL-MACROPHAGES

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.