IFN-gamma inhibition of TRAIL-induced IAP-2 upregulation, a possible mechanism of IFN-gamma-enhanced TRAIL-induced apoptosis.
IFN-gamma inhibition of TRAIL-induced IAP-2 upregulation, a possible mechanism of IFN-gamma-enhanced TRAIL-induced apoptosis.
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IFN-γ 抑制 TRAIL 诱导的 IAP-2 上调，这是 IFN-γ 增强 TRAIL 诱导细胞凋亡的可能机制。
DOI：
10.1006/bbrc.2002.6452
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Seol,Dai-Wu
中科院分区：
文献类型：
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作者：
Park,Sang-Youel;Billiar,TimothyR;Seol,Dai-Wu
肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）是TNF家族的II型跨膜细胞因子分子，是一种有效的细胞凋亡诱导剂。TNF家族成员的抗癌活性通常由干扰素(IFN)-γ调节。因此，我们研究了IFN-γ是否会增强trail诱导的细胞凋亡。我们将HeLa细胞暴露于IFN-γ中12小时，然后用重组TRAIL蛋白处理。经IFN-γ预处理的细胞未发生凋亡，TRAIL在处理3 h后诱导25%的细胞死亡。在经IFN-γ预处理的HeLa细胞中，TRAIL在3小时诱导细胞死亡70%以上，表明IFN-γ预处理使HeLa细胞对TRAIL诱导的凋亡敏感。我们研究了IFN-γ预处理可能调控的影响trail诱导的细胞凋亡的分子。Western blotting分析表明，TRAIL处理增加了IAP-2蛋白水平，IFN-γ预处理抑制了TRAIL蛋白对IAP-2蛋白的上调。我们的数据表明，TRAIL至少可以通过IAP-2同时激活凋亡诱导和抗凋亡机制。IFN-γ或TRAIL单独处理不会改变其他促或抗凋亡蛋白的表达，如DR4、DR5、FADD、Bax、IAP-1、XIAP、Bcl-2和Bcl-XL。我们的研究结果表明，IFN-γ可能通过阻止TRAIL诱导的IAP-2上调，使HeLa细胞对TRAIL诱导的凋亡敏感，IFN-γ可能通过这一机制参与TRAIL蛋白的抗癌治疗。
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane cytokine molecule of TNF family and a potent inducer of apoptosis. The anticancer activities of TNF family members are often modulated by interferon (IFN)-γ. Thus, we investigated whether IFN-γ enhances TRAIL-induced apoptosis. We exposed HeLa cells to IFN-γ for 12 h and then treated with recombinant TRAIL protein. No apoptosis was induced in cells pretreated with IFN-γ, and TRAIL induced 25% cell death after 3 h treatment. In HeLa cells pretreated with IFN-γ, TRAIL induced cell death to more than 70% at 3 h, indicating that IFN-γ pretreatment sensitized HeLa cells to TRAIL-induced apoptosis. We investigated molecules that might be regulated by IFN-γ pretreatment that would affect TRAIL-induced apoptosis. Western blotting analyses demonstrated that TRAIL treatment increased the level of IAP-2 protein and IFN-γ pretreatment inhibited the upregulation of IAP-2 protein by TRAIL protein. Our data indicate that TRAIL can signal to activate both apoptosis induction and antiapoptotic mechanism, at least, through IAP-2 simultaneously. IFN-γ or TRAIL treatment alone did not change expression of other pro- or antiapoptotic proteins such as DR4, DR5, FADD, Bax, IAP-1, XIAP, Bcl-2, and Bcl-XL. Our findings suggest that IFN-γ may sensitize HeLa cells to TRAIL-induced apoptosis by preventing TRAIL-induced IAP-2 upregulation, and IFN-γ may play a role in anticancer therapy of TRAIL protein through such mechanism.