Disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles in mice
Disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles in mice
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DOI：
10.1016/j.clim.2008.05.005
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发表时间：
2008-09-01
影响因子：
8.6
通讯作者：
Sugawara, Isamu
中科院分区：
文献类型：
--
作者：
Li, Ying Ji;Takizawa, Hajime;Sugawara, Isamu
为了验证我们的假设，即柴油机尾气颗粒物（DEP）诱导的氧化应激和宿主的抗氧化反应在DEP诱导的气道炎症性疾病的发展中起着关键作用，C57 BL/6核红细胞2 P45相关因子2（Nrf 2（-/-））敲除（Nrf 2（-/-））和野生型小鼠暴露于低剂量DEP 7小时/天，5天/周，共8周。暴露于低剂量DEP的Nrf 2（-/-）小鼠的气道高反应性和淋巴细胞和嗜酸性粒细胞计数显著增加，BAL液中IL-12和IL-13以及胸腺和活化调节趋化因子（TARC）的浓度也显著增加。相反，野生型小鼠中抗氧化酶基因的表达显著高于Nrf 2（-/-）小鼠。我们首次证明了Nrf 2的破坏增强了小鼠对吸入两剂量DEP诱导的气道炎症反应的易感性。这些结果有力地表明，DEP诱导的氧化应激和宿主的抗氧化反应在DEP诱导的气道炎症的发展中发挥了一定的作用。(C)2008年爱思唯尔公司All rights reserved.
To test our hypothesis that diesel exhaust particle (DEP)-induced oxidative stress and host antioxidant responses play a key role in the development of DEP-induced airway inflammatory diseases, C57BL/6 nuclear erythroid 2 P45-related factor 2 (Nrf2) knockout (Nrf2(-/-)) and wild-type mice were exposed to low-dose DEP for 7 h/day, 5 days/week, for 8 weeks. Nrf2(-/-) mice exposed to low-dose DEP showed significantly increased airway hyperresponsiveness and counts of lymphocytes and eosinophils, together with increased concentrations of IL-12 and IL-13, and thymus and activation-regulated chemokine (TARC), in BAL fluid than witd-type mice. In contrast, expression of antioxidant enzyme genes was significantly higher in wild-type mice than in Nrf2(-/-) mice. We have first demonstrated that disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by inhalation of tow-dose DEP in mice. These results strongly suggest that DEP-induced oxidative stress and host antioxidant responses play some role in the development of DEP-induced airway inflammation. (C) 2008 Elsevier Inc. All rights reserved.