Inhibition by auranofin of the production of prostaglandin E2 and nitric oxide in rat peritoneal macrophages.
In rat peritoneal macrophages, 12-O-tetradecanoylphorbol 13-acetate (TPA) (16.2 nM) stimulated production of both prostaglandin E2 and nitric oxide. TPA also increased the levels of mRNA for cyclooxygenase-2 and inducible nitric oxide synthase, suggesting that the increase in the production of prostaglandin E2 and nitric oxide is due to the increase in the levels of mRNA for cyclooxygenase-2 and inducible nitric oxide synthase, respectively. The TPA-induced increase in prostaglandin E2 production was partially inhibited by the inhibitor of nitric oxide synthase L-N(G)-monomethyl-L-arginine acetate (L-NMMA), and the TPA-induced increase in nitric oxide production was partially inhibited by the cyclooxygenase inhibitor indomethacin, suggesting that both the production of prostaglandin E2 and nitric oxide in TPA-stimulated macrophages is influenced by each other. The orally active chrysotherapeutic agent auranofin, at 3 and 10 microM, inhibited the TPA-stimulated production of prostaglandin E2 and nitric oxide, and suppressed the TPA-induced increase in the levels of mRNA for cyclooxygenase-2 and inducible nitric oxide synthase. These findings indicate that the inhibition by auranofin of the TPA-stimulated production of prostaglandin E2 and nitric oxide is due to the decrease in the levels of mRNA for cyclooxygenase-2 and inducible nitric oxide synthase, respectively, and the interaction of the production between prostaglandin E2 and nitric oxide may partly be involved in the mechanism for the inhibition by auranofin of the production of both prostaglandin E2 and nitric oxide.
Yamashita
M
M
Department of Pathophysiological Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
Ichinowatari
G
G
Yamaki
K
K
Ohuchi
K
K
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001310:Auranofin / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D018501:Antirheumatic Agents; D002273:Carcinogens; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001310:Auranofin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin