NF-κB regulation of endothelial cell function during LPS-induced toxemia and cancer
NF-κB regulation of endothelial cell function during LPS-induced toxemia and cancer
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DOI：
10.1172/jci27392
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发表时间：
2006-11-01
影响因子：
15.9
通讯作者：
Schindler, Christian
中科院分区：
文献类型：
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作者：
Kisseleva, Tatiana;Song, Li;Schindler, Christian
转录因子nf - κ B是体内平衡生长和炎症的重要调节因子。尽管基因靶向研究已经揭示了NF-kappa B的重要作用，但它们因成分冗余和致死表型而变得复杂。为了研究NF-kappa B在内皮组织中的作用，我们构建了Tie2启动子/增强子i kappa B α (S32A/S36A)转基因小鼠。这些小鼠生长正常，但对lps诱导的毒血症表现出增强的敏感性，特别是血管通透性和细胞凋亡的增加。此外，在转基因小鼠中，B16-BL6肿瘤的生长明显更具攻击性，这强调了NF-kappa B在癌症稳态反应中的新作用。转基因小鼠肿瘤血管分布广泛，组织混乱。这与紧密连接形成的显著缺失相关，表明NF-kappa B在维持血管完整性和应激反应中起重要作用。
The transcription factor NF-kappa B is an important regulator of homeostatic growth and inflammation. Although gene-targeting studies have revealed important roles for NF-kappa B, they have been complicated by component redundancy and lethal phenotypes. To examine the role of NF-kappa B in endothelial tissues, Tie2 promoter/enhancer-I kappa B alpha(S32A/S36A) transgenic mice were generated. These mice grew normally but exhibited enhanced sensitivity to LPS-induced toxemia, notable for an increase in vascular permeability and apoptosis. Moreover, B16-BL6 tumors grew significantly more aggressively in transgenic mice, underscoring a new role for NF-kappa B in the homeostatic response to cancer. Tumor vasculature in transgenic mice was extensive and disorganized. This correlated with a marked loss in tight junction formation and suggests that NF-kappa B plays an important role in the maintenance of vascular integrity and response to stress.