EXTENSION OF THE LIFE-SPAN OF HUMAN ENDOTHELIAL-CELLS BY AN INTERLEUKIN-1-ALPHA ANTISENSE OLIGOMER

EXTENSION OF THE LIFE-SPAN OF HUMAN ENDOTHELIAL-CELLS BY AN INTERLEUKIN-1-ALPHA ANTISENSE OLIGOMER
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DOI:
10.1126/science.2218499
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发表时间:
1990-09-28
期刊:
影响因子:
56.9
通讯作者:
MACIAG, T
MACIAG, T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
MAIER, JAM;VOULALAS, P;MACIAG, T

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人二倍体内皮细胞的增殖潜力是有限的,并且体外细胞衰老伴随着内皮细胞对外源性生长因子应答的失败。显示衰老的人内皮细胞含有大量的细胞因子白细胞介素-1 α的转录物。(IL-1 α),体外内皮细胞增殖的有效抑制剂。相反,转化的人内皮细胞不含可检测的IL-1 α。信使RNA。 用人IL-1 α的反义寡脱氧核苷酸处理人内皮细胞群转录本在体外阻止细胞衰老并延长细胞的增殖寿命。去除IL-1 α。反义寡聚体导致衰老表型的产生和增殖潜能的丧失。这些数据表明,体外人内皮细胞衰老是由IL-1 α的潜在细胞内活性调节的动态过程。
The proliferative potential of human diploid endothelial cells is finite, and cellular senescence in vitro is accompanied by the failure of the endothelial cell to respond to exogenous growth factors. Senescent human endothelial cells were shown to contain high amounts of the transcript for the cytokine interleukin-1.alpha. (IL-1.alpha.), a potent inhibitor of endothelial cell proliferation in vitro. In contrast, transformed human endothelial cells did not contain detectable IL-1.alpha. messenger RNA. Treatment of human endothelial cell populations with an antisense oligodeozynucleotide to the human IL-1.alpha. transcript prevented cell senescence and extended the proliferative life-span of the cells in vitro. Removal of the IL-1.alpha. antisense oligomer resulted in the generation of the senescent phenotype and loss of proliferative potential. These data suggest that human endothelial cell senescence in vitro is a dynamic process regulated by the potential intracellular activity of IL-1.alpha.