PYRIDINYL IMIDAZOLES INHIBIT IL-1 AND TNF PRODUCTION AT THE PROTEIN LEVEL

被引:114
作者
YOUNG, P [1 ]
MCDONNELL, P [1 ]
DUNNINGTON, D [1 ]
HAND, A [1 ]
LAYDON, J [1 ]
LEE, J [1 ]
机构
[1] SMITHKLINE BEECHAM PHARMACEUT,DEPT CELLULAR BIOCHEM,KING OF PRUSSIA,PA 19406
来源
AGENTS AND ACTIONS | 1993年 / 39卷
关键词
D O I
10.1007/BF01972723
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The mechanism by which SK&F 86002 and other pyridinyl imidazoles inhibit the production of IL-1 and TNF from LPS-stimulated human monocytes was examined. Inhibition of IL-1 and TNF production was found to depend on the time of addition of SK&F 86002, with diminishing effect when added more than 2 h after LPS stimulation. Analysis of Western blots confirmed that both intracellular IL-1beta and extracellular TNF were significantly reduced in response to SK&F 86002, but these reductions were not paralleled by changes in IL-1 and TNF mRNA. S-35 methionine pulse and pulse-chase studies on IL-1 biosynthesis suggest that significant inhibition by SK&F 86002 and related compounds occurs at the translational level.
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页码:C67 / C69
页数:3
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