Libby P, Ordovas J M, Auger K R, Robbins A H, Birinyi L K, Dinarello C A
Am J Pathol. 1986 Aug;124(2):179-85.
Interleukin 1 (IL-1) can induce potentially pathogenic functions of vascular endothelial cells. This mediator was formerly thought to be produced primarily by activated macrophages. We report here that bacterial endotoxin and recombinant human tumor necrosis factor cause accumulation of IL-1 beta mRNA in adult human vascular endothelial cells. IL-1 alpha mRNA was also detected when endothelial cells were exposed to endotoxin under "superinduction" conditions in the presence of cycloheximide. Metabolic labeling of these cells during endotoxin stimulation demonstrated increased synthesis and secretion of immunoprecipitable IL-1 protein that comigrated electrophoretically with the predominant monocyte species. In parallel with increased IL-1 mRNA and protein, endothelial cells exposed to endotoxin also release biologically active IL-1 that was neutralized by anti-IL-1-antibody. Because bloodborne agents must traverse the endothelium before entering tissues, endothelial IL-1 production induced by microbial products or other injurious stimuli could initiate local responses to invasion. Endothelial cells are both a source of and target for IL-1; accordingly, this novel autocrine mechanism might play an early role in the pathogenesis of vasculitis, allograft rejection, and arteriosclerosis.
白细胞介素1（IL-1）可诱导血管内皮细胞产生潜在的致病功能。这种介质以前被认为主要由活化的巨噬细胞产生。我们在此报告，细菌内毒素和重组人肿瘤坏死因子可导致成人血管内皮细胞中IL-1β mRNA的积累。当内皮细胞在存在环己酰亚胺的“超诱导”条件下暴露于内毒素时，也检测到了IL-1α mRNA。在内毒素刺激期间对这些细胞进行代谢标记表明，可免疫沉淀的IL-1蛋白的合成和分泌增加，其在电泳中与主要的单核细胞种类迁移一致。与IL-1 mRNA和蛋白的增加同时，暴露于内毒素的内皮细胞也释放出具有生物活性的IL-1，该IL-1被抗IL-1抗体中和。由于血源性病原体在进入组织之前必须穿过内皮，因此微生物产物或其他损伤性刺激诱导的内皮IL-1产生可能引发对入侵的局部反应。内皮细胞既是IL-1的来源又是其靶标；因此，这种新的自分泌机制可能在血管炎、同种异体移植排斥和动脉粥样硬化的发病机制中起早期作用。
