Impaired pulmonary NF-κB activation in response to lipopolysaccharide in NADPH oxidase-deficient mice
Impaired pulmonary NF-κB activation in response to lipopolysaccharide in NADPH oxidase-deficient mice
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DOI：
10.1128/iai.69.10.5991-5996.2001
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发表时间：
2001-10-01
影响因子：
3.1
通讯作者：
Blackwell, TS
中科院分区：
文献类型：
--
作者：
Koay, MA;Christman, JW;Blackwell, TS
活性氧（ROS）被认为参与细胞内信号传导，包括转录因子NF-κ B的活化。我们通过利用缺乏NADPH氧化酶的p47（phox）组分的敲除小鼠（p47（phox-/-））来研究NADPH氧化酶在NF-κ B活化途径中的作用。将野生型（WT）对照和P47（phox-/-）小鼠用腹膜内（i. p.）大肠杆菌脂多糖（LPS）（5或20 μ g/g体重）。与p47（phox-/-）小鼠相比，在用20 μ g但不是5 μ g/g腹腔注射LPS处理90分钟后，WT小鼠肺组织核蛋白提取物中LPS诱导的NF-κ B结合活性和RelA的积累显著增加。在另一种肺部炎症模型中，与p47（phox-/-）小鼠相比，RelA核移位减少。用雾化LPS处理后的WT小鼠。与p47（phox-/-）小鼠中的NF-κ B活化相反，与WT小鼠相比，这些小鼠中LPS诱导的肺中巨噬细胞炎性蛋白2的产生和嗜中性粒细胞肺炎症没有减少。我们的结论是，LPS诱导的NF-κ B活化是缺乏的p47（phox-/-）小鼠的肺相比，野生型小鼠，但这种异常不会导致明显的改变，在急性炎症反应。
Reactive oxygen species (ROS) are thought to be involved in intracellular signaling, including activation of the transcription factor NF-kappaB. We investigated the role of NADPH oxidase in the NF-KB activation pathway by utilizing knockout mice (p47(phox-/-)) lacking the p47(phox) component of NADPH oxidase. Wild-type (WT) controls and P47(phox-/-) mice were treated with intraperitoneal (i.p.) Escherichia coli lipopolysaccharide (LPS) (5 or 20 mug/g of body weight). LPS-induced NF-kappaB binding activity and accumulation of RelA in nuclear protein extracts of lung tissue were markedly increased in WT compared to p47(phox-/-) mice 90 min after treatment with 20 but not 5 mug of i.p. LPS per g. In another model of lung inflammation, RelA nuclear translocation was reduced in p47(phox-/-) mice compared to. WT mice following treatment with aerosolized LPS. In contrast to NF-kappaB activation in p47(phox-/-) mice, LPS-induced production of macrophage inflammatory protein 2 in the lungs and neutrophilic lung inflammation were not diminished in these mice compared to WT mice. We conclude that LPS-induced NF-KB activation is deficient in the lungs of p47(phox-/-) mice compared to WT mice, but this abnormality does not result in overt alteration in the acute inflammatory response.