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Pyridinyl imidazoles inhibit IL-1 and TNF production at the protein level |
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| Authors: | Young P. McDonnell P. Dunnington D. Hand A. Laydon J. Lee J. |
| Affiliation: | 1.Department of Molecular Genetics, SmithKline Beecham Pharmaceuticals, 19406-0939, King of Prussia, PA, USA ;2.Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, 19406-0939, King of Prussia, PA, USA ; |
| Abstract: | 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-1β 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.35S 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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