Inhibition of TPA-induced NF-kappaB nuclear translocation and production of NO and PGE2 by the anti-rheumatic gold compounds.
Auranofin, aurothioglucose and aurothiomalate (10 microM each) inhibited 12-O-tetradecanoylphorbol 13-acetate (TPA, 16.2 nM)-induced nuclear translocation of nuclear factor-kappa B (NF-kappaB), and production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in rat peritoneal macrophages when the cells were pre-incubated with each gold compound for 20 h. Without pre-incubation for 20 h, aurothioglucose and aurothiomalate, but not auranofin, failed to inhibit the TPA-induced NF-kappaB nuclear translocation and production of NO and PGE(2). Auranofin, aurothioglucose and aurothiomalate did not affect the direct binding of NF-kappaB to the DNA probe. It was suggested that these gold compounds inhibit the TPA-induced production of NO and PGE(2) by inhibiting the NF-kappaB nuclear translocation.
Yamashita
Masamichi
M
Department of Pathophysiological Science, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi 981-8558, Japan. may@tohoku-pharm.ac.jp
Ashino
Shigeru
S
Oshima
Yuko
Y
Kawamura
Shunsuke
S
Ohuchi
Kazuo
K
Takayanagi
Motoaki
M
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001310:Auranofin / Q000494:pharmacology; D006051:Aurothioglucose / Q000494:pharmacology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis; D006052:Gold Sodium Thiomalate / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D018501:Antirheumatic Agents; D016328:NF-kappa B; D006052:Gold Sodium Thiomalate; D006051:Aurothioglucose; D009569:Nitric Oxide; D001310:Auranofin; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate