Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells.
Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells.
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发表时间：
1986-08
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通讯作者：
P. Libby;J. Ordovás;K. Auger;A. Robbins;L. Birinyi;C. Dinarello
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作者：
P. Libby;J. Ordovás;K. Auger;A. Robbins;L. Birinyi;C. Dinarello
白细胞介素1（IL-1）可诱导血管内皮细胞的潜在致病功能。这种介质以前被认为主要由活化的巨噬细胞产生。我们在这里报告，细菌内毒素和重组人肿瘤坏死因子导致IL-1 β mRNA在成人血管内皮细胞的积累。在放线菌酮存在的“超诱导”条件下，当内皮细胞暴露于内毒素时，也检测到IL-1 α mRNA。这些细胞在内毒素刺激过程中的代谢标记表明，增加的合成和分泌的免疫可沉淀的IL-1蛋白，共迁移与主要的单核细胞物种。与增加的IL-1 mRNA和蛋白平行，暴露于内毒素的内皮细胞也释放生物活性IL-1，其被抗IL-1抗体中和。由于血源性因子在进入组织之前必须穿过内皮，因此微生物产物或其他有害刺激诱导的内皮IL-1产生可能会引发局部对入侵的反应。内皮细胞既是IL-1的来源又是IL-1的靶点;因此，这种新的自分泌机制可能在血管炎、同种异体移植排斥反应和动脉硬化的发病机制中发挥早期作用。
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.