Interleukin 1 induces interleukin 1. II. Recombinant human interleukin 1 induces interleukin 1 production by adult human vascular endothelial cells.
Interleukin 1 induces interleukin 1. II. Recombinant human interleukin 1 induces interleukin 1 production by adult human vascular endothelial cells.
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DOI：
10.4049/jimmunol.139.6.1911
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发表时间：
1987-09
影响因子：
4.4
通讯作者：
S. Warner;K. Auger;P. Libby
中科院分区：
文献类型：
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作者：
S. Warner;K. Auger;P. Libby
白介素1(IL-1)改变了几种潜在的致病内皮细胞(EC)功能。作者报道重组人IL-1(rIL-1)α(0.1~10 ng/ml)或IL-1-β(1~100 ng/ml)诱导成人大隐静脉内皮细胞IL-1-βmRNA水平呈浓度和时间依赖性增加。IL-1仅在放线菌酮(2微克/毫升)联合处理的EC中诱导IL-1-α基因的表达。IL-1-βmRNA的产生在暴露于rIL-1的1小时内开始，24小时后达到顶峰，此后下降。放线菌素D可抑制rIL-1处理的EC中IL-1mRNA的表达。IL-1还可诱导EC释放具有生物活性的IL-1，该作用可被放线菌酮(1微克/毫升)抑制。在胸腺细胞共刺激活性比较的基础上，rIL-1-α和rIL-1-β作为EC产生IL-1的诱导剂是相同的。用rIL-1刺激的EC产生前列腺素E2，它抑制其他类型细胞产生IL-1，并降低胸腺细胞对IL-1的反应性。当内皮细胞暴露于含有抑制前列腺素E2产生的消炎痛(1微克/毫升)的rIL-1时，检测到更多的rIL-1诱导的IL-1释放，尽管该抑制剂不影响IL-1-β的mRNA水平。IL-1诱导的IL-1产生不太可能是由组织培养上清液或IL-1制剂中的内毒素污染引起的，因为脂多糖(LPS)拮抗剂多粘菌素B(10微克/ml)可阻断EC内毒素诱导的IL-1产生，但不影响IL-1-β(100 ng/ml)对IL-1的释放。RIL-1-β对IL-1的诱导作用是热不稳定的，而加热的内毒素可刺激EC产生IL-1。在我们的培养中，IL-1的来源不是单核/巨噬细胞，因为在裂解贴壁外周血单核细胞的条件下，用抗单核细胞抗原Mo2的单抗处理EC，并不影响EC对内毒素(1微克/毫升)或rIL-1-β(100 ng/ml)产生IL-1。IL-1引起内皮功能改变的协调程序，增加对白细胞的粘附性和凝固性。IL-1诱导的成人内皮细胞IL-1基因表达可在动脉粥样硬化、血管炎和同种异体移植排斥反应等血管疾病的发病机制中提供正反馈机制。
Interleukin 1 (IL-1) alters several potentially pathogenic endothelial cell (EC) functions. The authors report here that recombinant human IL-1 (rIL-1) alpha (0.1 to 10 ng/ml) or IL-1-beta (1 to 100 ng/ml) induce concentration- and time-dependent increases in IL-1-beta mRNA levels in EC derived from adult human saphenous vein. rIL-1 induced IL-1-alpha mRNA only in EC treated concomitantly with cycloheximide (2 micrograms/ml). IL-1-beta mRNA production began within 1 hr of exposure to rIL-1, peaked after 24 hr, and declined thereafter. Actinomycin D prevented the appearance of IL-1 mRNA in rIL-1-treated EC. rIL-1 also induced the release of biologically active IL-1 from EC, which was inhibited by cycloheximide (1 microgram/ml). When compared on the basis of their activity in the thymocyte costimulation assay, rIL-1-alpha and rIL-1-beta were equipotent as inducers of IL-1 production by EC. EC stimulated with rIL-1 produced prostaglandin E2, which inhibits IL-1 production by other cell types and also decreases the responsiveness of thymocytes to IL-1. When EC were exposed to rIL-1 in the presence of indomethacin (1 microgram/ml), which blocked prostaglandin E2 production, greater amounts of rIL-1-induced IL-1 release were detected, although the inhibitor did not affect IL-1-beta mRNA levels. IL-1-induced IL-1 production was unlikely to be caused by endotoxin contamination of tissue culture media or IL-1 preparations, because the lipopolysaccharide (LPS) antagonist polymyxin B (10 micrograms/ml) blocked LPS-induced IL-1 production by EC but did not affect IL-1 release in response to rIL-1-beta (100 ng/ml). The IL-1-inducing property of rIL-1-beta was heat-labile, whereas heated LPS stimulated EC IL-1 production. The source of IL-1 in our cultures was not monocyte/macrophages, as treatment of EC with monoclonal antibody to the monocyte antigen Mo2 under conditions that lysed adherent peripheral blood monocytes did not affect production of IL-1 by EC in response to LPS (1 microgram/ml) or rIL-1-beta (100 ng/ml). IL-1 elicits a coordinated program of altered endothelial function that increases adhesiveness for leukocytes and coagulability. IL-1-induced IL-1 gene expression in human adult EC could thus provide a positive feedback mechanism in the pathogenesis of vascular disease including atherosclerosis, vasculitis, and allograft rejection.