Dual effects of auranofin on prostaglandin E2 production by rat peritoneal macrophages

European Journal of Pharmacology
M YamashitaK Ohuchi

Abstract

Incubation of rat peritoneal macrophages in medium containing various concentrations of auranofin (1, 3 and 10 microM) increased prostaglandin E2 production at 4 h in a concentration-dependent manner, in accordance with the increase in the release of [3H]arachidonic acid from membrane phospholipids. However, at 20 h, no stimulation of prostaglandin E2 production by auranofin was observed. When the peritoneal macrophages were incubated in the presence of 12-O-tetradecanoylphorbol 13-acetate (TPA), thapsigargin or A23187, prostaglandin E2 production at 4 and 20 h was enhanced. The stimulator-induced prostaglandin E2 production at 20 h was suppressed by 10 microM of auranofin. Western blot analysis demonstrated that auranofin inhibited the induction of cyclooxygenase 2 by TPA, thapsigargin or A23187 at 4 and 20 h. The level of cyclooxygenase 1 did not change by treatment with these stimulators in the presence or absence of auranofin. These findings suggest that auranofin has dual effects on prostaglandin E2 production: without stimulation, auranofin increases prostaglandin E2 production at 4 h due to the increased release of arachidonic acid which is converted to prostaglandin E2 mainly by cyclooxygenase 1, but inhibits the stimul...Continue Reading

References

Feb 1, 1975·Analytical Biochemistry·C Wang, R L Smith
Dec 1, 1992·The Journal of Experimental Medicine·A S NeishT Collins
May 15, 1989·Biochemical Pharmacology·M Peters-Golden, C Shelly
Dec 30, 1983·The American Journal of Medicine·M E WengerW J Blechman

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Citations

Sep 12, 2012·Inflammopharmacology·J M MadeiraA Klegeris
Mar 11, 2003·The Journal of Pharmacy and Pharmacology·Gabriel SertsouThomas Rades
Oct 2, 2001·The Journal of Pharmacy and Pharmacology·Y P KimK Ohuchi
Mar 13, 2003·The Journal of Pharmacy and Pharmacology·Masamichi YamashitaMotoaki Takayanagi

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