p40phox expression regulates neutrophil recruitment and function during the resolution phase of intestinal inflammation.
p40phox expression regulates neutrophil recruitment and function during the resolution phase of intestinal inflammation.
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DOI：
10.4049/jimmunol.1103746
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发表时间：
2012-10-01
期刊：
影响因子：
--
通讯作者：
Xavier RJ
中科院分区：
文献类型：
--
作者：
Conway KL;Goel G;Sokol H;Manocha M;Mizoguchi E;Terhorst C;Bhan AK;Gardet A;Xavier RJ
NADPH 氧化酶是一种多亚基复合物，在吞噬作用过程中组装产生活性氧 (ROS)。该复合物的多个成分与慢性肉芽肿病和克罗恩病有关，凸显了 ROS 在调节宿主免疫反应中的重要性。在这项研究中，我们使用基因缺陷小鼠来阐明 NADPH 氧化酶复合物的一个亚基 p40phox 在肠道炎症期间如何发挥作用。我们发现 p40phox 缺乏会增强硫酸葡聚糖钠诱导的和先天免疫介导的小鼠结肠炎模型中的炎症。这种炎症的特征是严重的结肠组织损伤、促炎细胞因子增加和中性粒细胞募集增加。我们证明中性粒细胞在肠道炎症的恢复阶段至关重要，并且 p40phox 表达对于这种恢复是必需的。最后，利用综合生物信息学方法，我们发现 p40phox 缺乏会导致炎症过程中趋化因子受体 1 的上调和参与聚糖修饰的酶（包括岩藻糖基转移酶和唾液酸转移酶）的下调。我们认为 p40phox 缺陷通过中性粒细胞中这两条途径的失调来增强肠道炎症。
NADPH oxidase is a multi-subunit complex that assembles during phagocytosis to generate reactive oxygen species (ROS). Several components of this complex have been implicated in chronic granulomatous disease and Crohn’s disease, highlighting the importance of ROS in regulating host immune response. In this study, we use genetically deficient mice to elucidate how p40phox, one subunit of the NADPH oxidase complex, functions during intestinal inflammation. We show that p40phox deficiency enhances inflammation in both dextran sulfate sodium-induced and innate immune-mediated murine colitis models. This inflammation is characterized by severe colonic tissue injury, increased proinflammatory cytokines, and increased neutrophil recruitment. We demonstrate that neutrophils are essential during the recovery phase of intestinal inflammation and that p40phox expression is necessary for this restitution. Lastly, using an integrative bioinformatic approach, we show that p40phox deficiency leads to upregulation of chemokine receptor 1 and downregulation of enzymes involved in glycan modifications, including fucosyltransferases and sialyltransferases, during inflammation. We propose that p40phox deficiency enhances intestinal inflammation through the dysregulation of these two pathways in neutrophils.
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影响因子：
3.1
作者：
GIONCHETTI, P;CAMPIERI, M;BARBARA, L
通讯作者：
BARBARA, L
DOI：
10.1152/ajplung.00120.2006
发表时间：
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影响因子：
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作者：
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通讯作者：
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