Pyridinyl imidazoles inhibit IL-1 and TNF production at the protein level

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.

研究了SK&F 86002及其他吡啶基咪唑抑制脂多糖（LPS）刺激的人单核细胞产生白细胞介素 - 1（IL - 1）和肿瘤坏死因子（TNF）的机制。发现对IL - 1和TNF产生的抑制作用取决于SK&F 86002的添加时间，在LPS刺激2小时后添加时效果减弱。蛋白质印迹分析证实，细胞内的IL - 1β和细胞外的TNF在SK&F 86002作用下均显著减少，但这些减少与IL - 1和TNF的信使核糖核酸（mRNA）变化并不平行。对IL - 1生物合成进行的³⁵S甲硫氨酸脉冲标记和脉冲追踪研究表明，SK&F 86002及相关化合物在翻译水平产生显著抑制作用。