Growth‐inhibiting effect of tumor necrosis factor on human umbilical vein endothelial cells is enhanced with advancing age in vitro

Growth‐inhibiting effect of tumor necrosis factor on human umbilical vein endothelial cells is enhanced with advancing age in vitro
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体外肿瘤坏死因子对人脐静脉内皮细胞生长抑制作用随年龄增长而增强

DOI:
10.1002/jcp.1041420105
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发表时间:
1990
影响因子:
5.6
通讯作者:
M. Matsuo
M. Matsuo
中科院分区:
生物学2区
文献类型:
--
作者:
Y. Shimada;K. Kaji;Hideki Ito;K. Noda;M. Matsuo

文献摘要

被引文献

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我们观察了肿瘤坏死因子加或不加干扰素-γ(干扰素-γ)对体外培养的人脐静脉内皮细胞生长能力的影响。对照细胞在体外的生长和集落形成能力随着年龄的增长而减弱,特别是在后期(超过70-80%的生命周期完成)。研究发现,在任何体外年龄,肿瘤坏死因子处理都会抑制细胞的生长和集落形成效率。肿瘤坏死因子的作用随着体外年龄的增加而增加,表现为倍增时间更明显地增加,饱和密度减少,克隆形成效率降低。然而,肿瘤坏死因子受体的特性,包括解离常数和每细胞表面积上的肿瘤坏死因子结合位点数保持不变。干扰素-γ单独给药对细胞生长和集落形成的影响很小,但可增强肿瘤坏死因子的作用。干扰素-γ的增强作用也被发现依赖于体外的年龄;与肿瘤坏死因子在降低集落形成能力方面的协同作用仅在“老化”的细胞中观察到。这些结果表明,HUVECs对生长抑制因子和生长刺激因子的内在反应性在体外老化过程中发生了变化。
We have examined the effects of in vitro aging on the growth capacity of human umbilical vein endothelial cells (HUVECs) under the influence of tumor necrosis factor (TNF) with or without interferon‐γ (IFN‐γ). The growth and colony‐forming abilities of control cells were impaired with advancing age in vitro, especially at later stages (more than 70–80% of life span completed). It was found that treatment with TNF inhibited growth and colony‐forming efficiency at any in vitro age. The effects of TNF were shown to increase with increasing in vitro age, as reflected by a more pronounced increase in doubling times, a decrease in saturation density, and a reduction in colony‐forming efficiency. However, the characteristics of TNF receptors, including the dissociation constant, and the number of TNF‐binding sites per cell‐surface area remained rather constant. The effect of TNF was augmented by IFN‐γ at a dose that alone affected growth and colony formation only slightly. The augmentation by IFN‐γ was also found to depend on in vitro age; the synergy with TNF in the deterioration of colony‐forming ability was observed only in “aged” cells. These results suggest that the intrinsic responsiveness of HUVECs to growth‐inhibiting factors, as well as to growth‐stimulating factors, changes during aging in vitro.