NF-κB activation in response to toxical and therapeutical agents:: role in inflammation and cancer treatment
NF-κB activation in response to toxical and therapeutical agents:: role in inflammation and cancer treatment
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DOI：
10.1016/s0300-483x(00)00302-4
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发表时间：
2000-11-16
期刊：
影响因子：
4.5
通讯作者：
Merville, MP
中科院分区：
文献类型：
--
作者：
Bours, V;Bonizzi, G;Merville, MP
NF-κ B转录因子广泛表达并控制大量基因的表达。实验数据清楚地表明，NF-κ B是炎症反应的主要调节因子，通过控制促炎分子的表达来响应细胞因子、氧化应激和感染因子。我们证明了IL-1 β激活NF-κ B遵循三种不同的细胞特异性途径。此外，我们的研究表明，在一种炎症性疾病模型中，马复发性气道阻塞（RAO），NF-κ B基础活性的程度与肺功能障碍相关。NF-κ B活性的另一个作用是保护癌细胞免于凋亡，并可能参与对癌症治疗的抵抗。然而，我们没有观察到任何增加的细胞毒性与抗癌药物或TNF-α的细胞表达NF-κ B抑制剂治疗后。因此，我们可以得出结论，NF-κ B抑制凋亡可能是细胞类型和刺激依赖性的。需要进一步的研究来确定NF-κ B是否可以成为抗癌治疗的靶点。(C)2000爱思唯尔科学爱尔兰有限公司保留所有权利。
The NF-kappaB transcription factor is ubiquitously expressed and controls the expression of a large number of genes. Experimental data clearly indicate that NF-kappaB is a major regulator of the inflammatory reaction by controlling the expression of pro-inflammatory molecules in response to cytokines, oxidative stress and infectious agents. We demonstrated that NF-kappaB activation by IL-1 beta follows three distinct cell-specific pathways. Moreover, our studies indicated that in one model of inflammatory diseases, horse recurrent airway obstruction (RAO), the extent of NF-kappaB basal activity correlates with pulmonary dysfunction. Another role of NF-kappaB activity protects cancer cells against apoptosis and could participate in the resistance to cancer treatment. However, we did not observe any increased cytotoxicity after treatment with anticancer drugs or TNF-alpha of cells expressing a NF-kappaB inhibitor. Therefore, we can conclude that the inhibition of apoptosis by NF-kappaB is likely to be cell type and stimulus-dependent. Further studies are required to determine whether NF-kappaB could be a target for anticancer treatments. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.