Disruption of nuclear factor-interleukin-6, a transcription factor, results in severe mycobacterial infection.
Disruption of nuclear factor-interleukin-6, a transcription factor, results in severe mycobacterial infection.
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核因子白细胞介素 6（一种转录因子）的破坏会导致严重的分枝杆菌感染。
DOI：
10.1016/s0002-9440(10)63977-6
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
S. Akira
中科院分区：
文献类型：
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作者：
I. Sugawara;S. Mizuno;H. Yamada;M. Matsumoto;S. Akira
核因子-白细胞介素-6（NF-IL-6）是几种核转录因子（NF-IL-6、NF-κB、PU. 1、干扰素调节因子1、Egr-1和Stat-1）之一。NF-IL-6和NF-κB在巨噬细胞中表达，并被细菌脂多糖诱导。为了评估NF-IL-6是否是对分枝杆菌感染的炎性免疫应答所必需的，其中上皮样巨噬细胞包含主要细胞群体，我们产生了NF-IL-6敲除（KO）突变小鼠。这些小鼠经空气感染结核分枝杆菌菌株诱导播散性结核，但无肉芽肿形成，尽管与野生型小鼠相比，干扰素-γ、肿瘤坏死因子-α和白细胞介素-12 mRNA表达水平在正常范围内。与野生型小鼠相比，这些小鼠的中性粒细胞产生的O2−和对分枝杆菌的杀伤严重受损。我们的结论是，NF-IL-6是一个关键的转录因子在分枝杆菌控制以及在粒细胞集落刺激因子诱导导致中性粒细胞活化。
Nuclear factor-interleukin-6 (NF-IL-6) is one of several nuclear transcription factors (NF-IL-6, NF-κB, PU.1, interferon-regulatory factor 1, Egr-1, and Stat-1). NF-IL-6 and NF-κB are expressed in macrophages and is induced by bacterial lipopolysaccharides. To evaluate whether NF-IL-6 is required for the inflammatory immune response to mycobacterial infection, in which epithelioid macrophages comprise the leading cell population, we generated NF-IL-6 knockout (KO) mutant mice. Airborne infection of these mice with Mycobacterium tuberculosis strains induced disseminated tuberculosis lacking granuloma formation, although interferon-γ, tumor necrosis factor-α, and interleukin-12 mRNA expression levels were within the normal range compared with those of wild-type mice. Generation of O2−and mycobacterial killing by neutrophils from these mice were impaired severely compared with wild-type mice. We conclude that NF-IL-6 is a critical transcription factor in mycobacterial control as well as in granulocyte-colony stimulating factor induction resulting in neutrophil activation.