Title: Effects of Chrisotherapeutic Gold Compounds on Prostaglandin E2 Production
Volume: 2
Issue: 3
Author(s): Masamichi Yamashita, Kazuo Ohuchi and Motoaki Takayanagi
Affiliation:
Keywords:
auranofin, aurothioglucose, aurothiomalate, chrisotherapeutic gold compounds;, macrophage, nuclear factor-kappa b
Abstract: The mechanism of action of anti-rheumatic gold compounds on 12-Otetradecanoylphorbol 13-acetate (TPA)-induced prostaglandin E2 (PGE2) production in rat peritoneal macrophages were examined. Auranofin (AF) at 3-10 μM inhibited TPAinduced PGE2 production in a concentration-dependent manner. In the pharmacological experiments , prostaglandin G / H synthase (PGHS)-2-dependent PGE2 production was inhibited by 10 μM of AF. The enzyme activities of both PGHS-1 and PGHS-2 were not affected by the 10 μM AF. Other gold compounds, aurothioglucose (ATG) and aurothiomalate (ATM) did not inhibit PGE2 production at 10 μM. AF decreased the PGHS-2 protein content, but had no effect on the PGHS-1 protein content. AF at 3-10 μM decreased the PGHS-2 messenger RNA (mRNA) level by RT-PCR determination. Then, the effect of AF on nuclear factor kappa B (NF-κB), one of the transcription factors known to regulate transcription of a group of proinflammatory proteins, was determined. AF at 1-10 μM inhibited nuclear translocation of NF-κB in a concentration-dependent manner. ATG and ATM at 10 μM did not inhibit NF-κB nuclear translocation, but with 20 h preincubation, ATG and ATM inhibited PGE2 production and NF-κB nuclear translocation. AF, ATG, and ATM did not affect the binding of NF-κB to its specific DNA. These observations may suggest that the effects of gold compounds on the inhibition of NF-κB nuclear translocation plays one of the major role in its anti-inflammatory effects in rat peritoneal macrophages.
