Gadjeva Mihaela, Wang Yanyan, Horwitz Bruce H
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Eur J Immunol. 2007 Sep;37(9):2509-17. doi: 10.1002/eji.200737186.
Mice which lack the p50 subunit of NF-kappaB and are heterozygous for the p65 subunit (3X mice), are exquisitely sensitive to LPS-induced shock. Here, we demonstrate that prior to becoming moribund, 3X mice challenged with LPS develop a profound enteropathy. The enteropathy is characterized by defects in intestinal barrier function, increased epithelial apoptosis, and deregulated intestinal cytokine gene expression. The defect that sensitizes 3X mice to LPS-induced enteropathy is located within the innate immune compartment, as LPS induced similar findings in 3X mice lacking lymphocytes (3X/RAG). TNF-alpha depletion ameliorated the ability of LPS to induce pathology and TNF-alpha was able to independently induce similar findings, suggesting that TNF-alpha plays a critical role in the development of LPS-induced pathology in these mice. These data highlight that NF-kappaB subunits have essential functions in regulating intestinal homeostasis during acute inflammation.
缺乏核因子-κB p50亚基且p65亚基为杂合子的小鼠（3X小鼠）对脂多糖（LPS）诱导的休克极为敏感。在此，我们证明，在濒死之前，用LPS攻击的3X小鼠会出现严重的肠病。这种肠病的特征是肠道屏障功能缺陷、上皮细胞凋亡增加以及肠道细胞因子基因表达失调。使3X小鼠对LPS诱导的肠病敏感的缺陷位于天然免疫区室，因为LPS在缺乏淋巴细胞的3X小鼠（3X/RAG）中诱导出了类似的结果。肿瘤坏死因子-α（TNF-α）的耗竭改善了LPS诱导病理变化的能力，并且TNF-α能够独立诱导出类似的结果，这表明TNF-α在这些小鼠LPS诱导的病理发展中起关键作用。这些数据突出表明，核因子-κB亚基在急性炎症期间调节肠道内环境稳定方面具有重要功能。
