REQUIREMENT FOR TRANSCRIPTION FACTOR IRF-1 IN NO SYNTHASE INDUCTION IN MACROPHAGES
REQUIREMENT FOR TRANSCRIPTION FACTOR IRF-1 IN NO SYNTHASE INDUCTION IN MACROPHAGES
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DOI：
10.1126/science.7510419
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发表时间：
1994-03-18
期刊：
影响因子：
56.9
通讯作者：
VILCEK, J
中科院分区：
文献类型：
--
作者：
KAMIJO, R;HARADA, H;VILCEK, J
由巨噬细胞产生的一氧化氮（NO）对于杀死细胞内感染因子是重要的。干扰素（IFN）-γ和脂多糖通过转录上调诱导型NO合酶（iNOS）刺激NO产生。来自靶向破坏IFN调节因子-1（IRF-1）基因的小鼠（IRF-1（-/-）小鼠）的巨噬细胞在响应刺激时产生很少或不产生NO，并且合成几乎不可检测的iNOS信使RNA。两个相邻的IRF-1的反应元件被确定在iNOS启动子。IRF-1（-/-）小鼠的牛分枝杆菌（BCG）感染比野生型小鼠更严重。因此，IRF-1是小鼠巨噬细胞中iNOS激活所必需的。
Production of nitric oxide (NO) by macrophages is important for the killing of intracellular infectious agents. Interferon (IFN)-gamma and lipopolysaccharide stimulate NO production by transcriptionally up-regulating the inducible NO synthase (iNOS). Macrophages from mice with a targeted disruption of the IFN regulatory factor-1 (IRF-1) gene (IRF-1(-/-) mice) produced little or no NO and synthesized barely detectable iNOS messenger RNA in response to stimulation. Two adjacent IRF-1 response elements were identified in the iNOS promoter. Infection with Mycobacterium bovis (BCG) was more severe in IRF-1(-/-) mice than in wild-type mice. Thus, IRF-1 is essential for iNOS activation in murine macrophages.