Pyridinyl imidazoles inhibit IL-1 and TNF production at the protein level
P Young, P McDonnell, D Dunnington, A Hand… - Agents and actions, 1993 - Springer
P Young, P McDonnell, D Dunnington, A Hand, J Laydon, J Lee
Agents and actions, 1993•SpringerThe 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 …
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 …
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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