TARGETED DISRUPTION OF THE NF-IL6 GENE DISCLOSES ITS ESSENTIAL ROLE IN BACTERIA KILLING AND TUMOR-CYTOTOXICITY BY MACROPHAGES
TARGETED DISRUPTION OF THE NF-IL6 GENE DISCLOSES ITS ESSENTIAL ROLE IN BACTERIA KILLING AND TUMOR-CYTOTOXICITY BY MACROPHAGES
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DOI：
10.1016/0092-8674(95)90418-2
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发表时间：
1995-01-27
期刊：
影响因子：
64.5
通讯作者：
KISHIMOTO, T
中科院分区：
文献类型：
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作者：
TANAKA, T;AKIRA, S;KISHIMOTO, T
为了研究NF-IL6在体内的作用，我们通过基因打靶的方法产生了NF-IL6(-/-)小鼠。NF-IL6(-/-)小鼠对单核细胞增多性李斯特菌高度易感。电子显微镜观察显示，在NF-IL6(-/-)小鼠激活的巨噬细胞中，大量病原体从吞噬小体逃逸到细胞质中。此外，来自NF-IL6(-/-)小鼠的巨噬细胞的肿瘤细胞毒性严重受损。然而，参与巨噬细胞激活的细胞因子，如肿瘤坏死因子和干扰素-γ，在NF-IL6(-/-)小鼠中正常诱导。野生型和NF-IL6(-/-)小鼠的巨噬细胞产生一氧化氮(NO)的程度相似。这些结果证明了核因子-IL6在巨噬细胞杀菌和杀瘤活性中的关键作用，以及这些活性的非独立机制的存在。我们还证明了在巨噬细胞和成纤维细胞中，核因子-IL6对于诱导G-CSF是必不可少的。
To investigate the role of NF-IL6 in vivo, we have generated NF-IL6 (-/-) mice by gene targeting. NF-IL6 (-/-) mice were highly susceptible to infection by Listeria monocytogenes. Electron microscopic observation revealed the escape of a large number of pathogens from the phagosome to the cytoplasm in activated macrophages from NF-IL6 (-/-) mice. Furthermore, the tumor cytotoxicity of macrophages from NF-IL6 (-/-) mice was severely impaired. However, cytokines involved in macrophage activation, such as TNF and IFN gamma, were induced normally in NF-IL6 (-/-) mice. Nitric oxide (NO) formation was induced to a similar extent in macrophages from both wild-type and NF-IL6 (-/-) mice. These results demonstrate the crucial role of NF-IL6 in macrophage bactericidal and tumoricidal activities as well as the existence of a NO-independent mechanism of these activities. We also demonstrate that NF-IL6 is essential for the induction of G-CSF in macrophages and fibroblasts.