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首页> 外文期刊>Molecular and Cellular Biology >IkappaBalpha deficiency results in a sustained NF-kappaB response and severe widespread dermatitis in mice.
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IkappaBalpha deficiency results in a sustained NF-kappaB response and severe widespread dermatitis in mice.

机译：IkappaBalpha缺乏会导致持续的NF-kappaB反应和严重的广泛性皮炎。

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The ubiquitous transcription factor NF-kappaB is an essential component in signal transduction pathways, in inflammation, and in the immune response. NF-kappaB is maintained in an inactive state in the cytoplasm by protein-protein interaction with IkappaBalpha. Upon stimulation, rapid degradation of IkappaBalpha allows nuclear translocation of NF-kappaB. To study the importance of IkappaBalpha in signal transduction, IkappaBalpha-deficient mice were derived by gene targeting. Cultured fibroblasts derived from IkappaBalpha-deficient embryos exhibit levels of NF-kappaB1, NF-kappaB2, RelA, c-Rel, and IkappaBbeta similar to those of wild-type fibroblasts. A failure to increase nuclear levels of NF-kappaB indicates that cytoplasmic retention of NF-kappaB may be compensated for by other IkappaB proteins. Treatment of wild-type cells with tumor necrosis factor alpha (TNF-alpha) resulted in rapid, transient nuclear localization of NF-kappaB. IkappaBalpha-deficient fibroblasts are also TNF-alpha responsive, but nuclear localization of NF-kappaB is prolonged, thus demonstrating that a major irreplaceable function Of IkappaBalpha is termination of the NF-kappaB response. Consistent with these observations, and with IkappaBalpha and NF-kappaB's role in regulating inflammatory and immune responses, is the normal development Of IkappaBalpha-deficient mice. However, growth ceases 3 days after birth and death usually occurs at 7 to 10 days of age. An increased percentage of monocytes/macrophages was detected in spleen cells taken from 5-, 7-, and 9-day-old pups. Death is accompanied by severe widespread dermatitis and increased levels of TNF-alpha mRNA in the skin.
机译：普遍存在的转录因子NF-κB是信号转导途径，炎症和免疫反应中的重要组成部分。 NF-kappaB通过与IkappaBalpha的蛋白质相互作用而保持在细胞质中的非活性状态。刺激后，IkappaBalpha的快速降解允许NF-kappaB的核易位。为了研究IkappaBalpha在信号转导中的重要性，通过基因定位衍生了IkappaBalpha缺陷小鼠。衍生自IkappaBalpha缺陷胚胎的培养成纤维细胞显示出与野生型成纤维细胞相似的NF-kappaB1，NF-kappaB2，RelA，c-Rel和IkappaBbeta水平。无法增加NF-κB的核水平表明NF-κB的胞质保留可能被其他IkappB蛋白补偿。用肿瘤坏死因子α（TNF-alpha）处理野生型细胞导致NF-κB的快速，瞬时核定位。缺乏IkappaBalpha的成纤维细胞也对TNF-alpha有反应，但NF-kappaB的核定位得以延长，因此证明了IkappaBalpha的主要不可替代功能是NF-kappaB反应的终止。与这些观察结果一致，并且与IkappaBalpha和NF-kappaB在调节炎症和免疫反应中的作用一致，是IkappaBalpha缺陷小鼠的正常发育。然而，生长在出生后3天就停止了，死亡通常发生在7至10天的年龄。从5、7和9天大的幼仔中取出的脾细胞中检测到单核细胞/巨噬细胞的百分比增加。死亡伴随着严重的广泛性皮炎和皮肤中TNF-αmRNA水平的升高。

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