Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced chemokine release in both TRAIL-resistant and TRAIL-sensitive cells via nuclear factor kappa B
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced chemokine release in both TRAIL-resistant and TRAIL-sensitive cells via nuclear factor kappa B
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DOI：
10.1111/j.1742-4658.2008.06809.x
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发表时间：
2009-01-01
期刊：
影响因子：
5.4
通讯作者：
Zheng, Dexian
中科院分区：
文献类型：
--
作者：
Tang, Wanhu;Wang, Weimin;Zheng, Dexian
肿瘤坏死因子相关凋亡诱导配体（TRAIL）可诱导多种肿瘤细胞凋亡，但在大多数正常细胞中不诱导凋亡，因其在肿瘤治疗中的潜在应用而引起广泛关注。最近，越来越多的证据表明，TRAIL参与炎症，尽管许多证据是有争议的。在这篇文章中，它表明，TRAIL诱导CXCL 2，CCL 4和CCL 20的分泌，在核因子κ B依赖的方式。肿瘤坏死因子受体相关死亡结构域蛋白（TRADD）和肿瘤坏死因子受体相关因子2的显性负性结构不能阻断TRAIL诱导的趋化因子上调，TRADD的显性负性结构甚至可以增强TRAIL触发的信号。使用小干扰RNA，受体相互作用蛋白已被证明是必需的TRAIL诱导的趋化因子释放。此外，已经证明p38丝裂原活化蛋白激酶参与TRAIL诱导的趋化因子释放，而对核因子κ B活化没有任何影响，这表明一些未知的转录因子可能被TRAIL激活。使用异种移植肿瘤模型，已经说明TRAIL也可以在体内诱导趋化因子释放。尽管这些由TRAIL诱导的趋化因子是炎性趋化因子，但它们的功能并不局限于炎症，需要进一步研究。我们的研究结果表明，应注意TRAIL治疗的副作用，不仅在TRAIL耐药，而且在TRAIL敏感的肿瘤细胞。
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of tumour cells, but not in most normal cells, and has attracted considerable attention for its potential use in cancer therapy. Recently, increasing evidence has shown that TRAIL is involved in inflammation, although much of this evidence is controversial. In this article, it is shown that TRAIL induces CXCL2, CCL4 and CCL20 secretion in a nuclear factor kappa B-dependent manner. The dominant negative constructs of tumour necrosis factor receptor-associated death domain protein (TRADD) and tumour necrosis factor receptor-associated factor 2 are unable to block TRAIL-induced chemokine up-regulation, and the dominant negative construct of TRADD may even enhance TRAIL-triggered signals. Using small interfering RNA, receptor interacting protein has been demonstrated to be essential for TRAIL-induced chemokine release. Furthermore, it has been demonstrated that p38 mitogen-activated protein kinase is involved in TRAIL-induced chemokine release without any effects on nuclear factor kappa B activation, suggesting that some unknown transcription factors may be activated by TRAIL. Using a xenograft tumour model, it has been illustrated that TRAIL can also induce chemokine release in vivo. Although these chemokines induced by TRAIL are inflammatory chemokines, their functions are not restricted to inflammation and require further examination. Our results indicate that attention should be paid to the side-effects of TRAIL treatment, not only in TRAIL-resistant but also in TRAIL-sensitive tumour cells.