Cytokine-induced nuclear factor kappa B activation promotes the survival of developing neurons
Cytokine-induced nuclear factor kappa B activation promotes the survival of developing neurons
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DOI：
10.1083/jcb.148.2.325
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发表时间：
2000-01-24
影响因子：
7.8
通讯作者：
Davies, AM
中科院分区：
文献类型：
--
作者：
Middleton, G;Hamanoue, M;Davies, AM
纤毛神经营养因子（CNTF）、白血病抑制因子（LIF）、心营养因子-1 （CT-1）和白细胞介素6 （IL-6）是一组结构相关的细胞因子，可促进周围神经系统中神经元亚群的存活，但这些细胞因子激活的阻止神经元凋亡的信号通路尚不清楚。在这里，我们发现这些细胞因子在依赖细胞因子的发育感觉神经元中激活nf - κ B。用超抑制因子I kappa B- α蛋白阻止NF-kappa B激活可显著减少在细胞因子存在下存活的神经元数量，但对相同神经元对脑源性神经营养因子（BDNF）的存活反应没有影响，BDNF是一种与不同类型受体结合的不相关的神经营养因子。缺乏p65（NF-kappa B的转录活性亚基）的胚胎培养的细胞因子依赖性感觉神经元对细胞因子的存活能力明显受损，但对BDNF的反应正常。体内p65（-/-）胚胎中细胞因子依赖性神经元的凋亡增加，导致这些神经元的总数与野生型胚胎相比减少。这些结果表明，NF-kappa B在调节发育中的神经元对细胞因子的生存反应中起着关键作用。
Ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), and interleukin 6 (IL-6) comprise a group of structurally related cytokines that promote the survival of subsets of neurons in the developing peripheral nervous system, but the signaling pathways activated by these cytokines that prevent neuronal apoptosis are unclear. Here, we show that these cytokines activate NF-kappa B in cytokine-dependent developing sensory neurons. Preventing NF-kappa B activation with a super-repressor I kappa B-alpha protein markedly reduces the number of neurons that survive in the presence of cytokines, but has no effect on the survival response of the same neurons to brain-derived neurotrophic factors (BDNF), an unrelated neurotrophic factor that binds to a different class of receptors. Cytokine-dependent sensory neurons cultured from embryos that lack p65, a transcriptionally active subunit of NF-kappa B, have a markedly impaired ability to survive in response to cytokines, but respond normally to BDNF There is increased apoptosis of cytokine-dependent neurons in p65(-/-) embryos in vivo, resulting in a reduction in the total number of these neurons compared with their numbers in wild-type embryos. These results demonstrate that NF-kappa B plays a key role in mediating the survival response of developing neurons to cytokines.