Nrf2 Modulates Host Defense during Streptococcus pneumoniae Pneumonia in Mice.
Nrf2 Modulates Host Defense during Streptococcus pneumoniae Pneumonia in Mice.
复制标题
DOI：
10.4049/jimmunol.1600043
复制
发表时间：
2016-10-01
期刊：
影响因子：
--
通讯作者：
Doerschuk CM
中科院分区：
文献类型：
--
作者：
Gomez JC;Dang H;Martin JR;Doerschuk CM
nrf 2调节氧化应激的转录反应。这些研究测试了Nrf 2在S.在肺组织和募集的中性粒细胞中鉴定了Nrf 2依赖性基因和途径。在滴注S. pneumoniae或PBS。在6小时时，与WT小鼠相比，在Nrf 2缺失小鼠中招募较少的中性粒细胞，并且肺中剩余的细菌数量倾向于较少（p=0.06）。在未感染的肺中，与WT小鼠肺相比，Nrf 2 null中已经有53个基因差异表达，并且与WT小鼠相比，PBS处理的Nrf 2 null基因谱中涉及吞噬作用、Fc受体功能、补体和免疫球蛋白调节的基因集增强。这些结果表明，在Nrf 2敲除小鼠中，初始宿主防御增强，导致中性粒细胞的募集减少。在24小时，中性粒细胞募集更大。早期凋亡和晚期凋亡/坏死中性粒细胞的百分比相似。随着接种物数量的增加，Nrf 2基因敲除小鼠的死亡率从15%显著增加至31%和100%，而所有WT小鼠均存活，Nrf 2基因敲除小鼠的清除率存在缺陷，尤其是在中等剂量下。死亡是由于肺损伤增强和全身反应增强。基因分析鉴定了中性粒细胞和肺组织中差异调节的基因和途径，包括参与氧化还原应激反应、代谢、炎症、免疫调节途径和组织修复的基因和途径，为更大的组织损伤和增加的中性粒细胞蓄积的机制提供了见解。
Nrf2 regulates the transcriptional response to oxidative stress. These studies tested the role of Nrf2 during S. pneumoniae pneumonia and identified Nrf2-dependent genes and pathways in lung tissue and in recruited neutrophils. Nrf2 null and WT mice were studied at 6 and 24 h following instillation of S. pneumoniae or PBS. At 6 h, fewer neutrophils were recruited and the number of bacterial remaining in the lungs tended to be less (p=0.06) in the Nrf2 null compared to WT mice. In uninfected lungs, 53 genes were already differentially expressed in Nrf2 null compared to WT mouse lungs and gene sets involved in phagocytosis, Fc receptor function, complement and immunoglobulin regulation are enhanced in PBS-treated Nrf2 null gene profiles compared to those of WT mice. These results suggest that initial host defense is enhanced in Nrf2 null mice, resulting in less recruitment of neutrophils. At 24 h, neutrophil recruitment was greater. The percentages of early apoptotic and late apoptotic/necrotic neutrophils were similar. At increasing inoculum numbers, mortality strikingly increased from 15% to 31% and 100% in Nrf2 null mice, whereas all WT mice survived, and Nrf2 null mice had a defect in clearance, particularly at the intermediate dose. The mortality was due to enhanced lung injury and greater systemic response. Gene profiling identified differentially regulated genes and pathways in neutrophils and lung tissue, including those involved in redox stress response, metabolism, inflammation, immunoregulatory pathways and tissue repair, providing insight into the mechanisms for the greater tissue damage and increased neutrophil accumulation.
登录
查看更多内容
影响因子：
14.9
作者：
Malhotra D;Portales-Casamar E;Singh A;Srivastava S;Arenillas D;Happel C;Shyr C;Wakabayashi N;Kensler TW;Wasserman WW;Biswal S
通讯作者：
Biswal S
DOI：
10.1164/ajrccm.164.supplement_2.2106064
发表时间：
2001-11-15
影响因子：
24.7
作者：
Warburton, D;Tefft, D;Driscoll, B
通讯作者：
Driscoll, B
影响因子：
14.9
作者：
Chorley BN;Campbell MR;Wang X;Karaca M;Sambandan D;Bangura F;Xue P;Pi J;Kleeberger SR;Bell DA
通讯作者：
Bell DA
DOI：
10.1164/rccm.201102-0271oc
发表时间：
2011-10-15
影响因子：
24.7
作者：
Kong, Xiaoni;Thimmulappa, Rajesh;Biswal, Shyam
通讯作者：
Biswal, Shyam
影响因子：
3.8
作者：
Cho, Hye-Youn;Kleeberger, Steven R.
通讯作者：
Kleeberger, Steven R.