Involvement of trail/trail-R interaction in IFN-α-induced apoptosis of daudi B lymphoma cells
Involvement of trail/trail-R interaction in IFN-α-induced apoptosis of daudi B lymphoma cells
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DOI：
10.1006/cyto.2001.0873
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发表时间：
2001-05-21
期刊：
影响因子：
3.8
通讯作者：
Mizuguchi, J
中科院分区：
文献类型：
--
作者：
Oshima, K;Yanase, N;Mizuguchi, J
干扰素-α（IFN-α）至少部分通过诱导细胞凋亡对各种肿瘤发挥抗肿瘤作用，细胞凋亡是由肿瘤坏死因子（TNF）家族成员诱导的，包括Fas（CD95）和TNF相关细胞凋亡诱导配体（TRAIL）。在本研究中，我们使用Daudi B淋巴瘤细胞检查了TRAIL/TRAIL-R系统是否参与LFN-α诱导的细胞凋亡，IFN-α上调了通过流式细胞术和 RT-PCR 评估，12 小时内 TRAIL 的水平随时间增加直至 72 小时。LFN-α 增强了 Daudi 细胞中较低的 TRAIL-R1 和 TRAIL-R2 水平，增强的 TRAIL-R1/-R2 似乎起到死亡诱导分子的作用，因为 IFN-α 刺激的细胞更容易受到 TRAIL 诱导的细胞死亡的影响。 Daudi细胞或其衍生的培养物上清液显示出针对TRAIL敏感细胞系的细胞毒性，但不显示抗性细胞系的细胞毒性。此外，中和抗TRAIL单克隆抗体基本上阻止了诱导细胞凋亡之前的IFN-α诱导的线粒体膜电位降低。总之，IFN-α诱导的细胞凋亡似乎是由涉及TRAIL/TRAIL-R的自分泌和/或旁分泌环介导的。 (C) 2001 年学术出版社。
Interferon-alpha (IFN-alpha) exerts the anti-tumour effect on various tumours at least partly through induction of apoptosis, Apoptosis is induced by members of the tumour necrosis factor (TNF) family, including Fas (CD95) and TNF-related apoptosis-inducing ligand (TRAIL), In the present study, we examined whether the TRAIL/TRAIL-R system is involved in LFN-alpha -induced apoptosis using Daudi B lymphoma cells, IFN-alpha upregulated the expression of TRAIL within 12 h, as assessed by flow cytometry and RT-PCR, and the level increased with time until 72 h, The levels of both TRAIL-R1 and TRAIL-R2, low in Daudi cells, were enhanced by LFN-alpha, The enhanced TRAIL-R1/-R2 appeared to function as a death-inducing molecule since IFN-alpha -stimulated cells were more susceptible to TRAIL-induced cell death, The IFN-alpha -stimulated Daudi cells or their derived culture supernatants displayed cytotoxicity against TRAIL-sensitive, but not resistant lines, Moreover, the IFN-alpha -induced reduction in mitochondrial membrane potential preceding the induction of apoptosis was substantially prevented by neutralizing anti-TRAIL monoclonal antibody. Taken together, IFN-alpha -induced apoptosis appears to be mediated by the autocrine and/or paracrine loop involving TRAIL/TRAIL-R. (C) 2001 Academic Press.