Activation of NF-kappaB varies in different regions of the gastrointestinal tract during endotoxemia.
Activation of NF-kappaB varies in different regions of the gastrointestinal tract during endotoxemia.
复制标题
DOI：
10.1097/00024382-200014020-00007
复制
发表时间：
2000-08
期刊：
影响因子：
3.1
通讯作者：
T. Pritts;T. Pritts;M. Moon;Quan Wang;Quan Wang;Eric S. Hungness;Eric S. Hungness;A. Salzman;Josef E. Fischer;P. Hasselgren;P. Hasselgren
中科院分区：
文献类型：
--
作者：
T. Pritts;T. Pritts;M. Moon;Quan Wang;Quan Wang;Eric S. Hungness;Eric S. Hungness;A. Salzman;Josef E. Fischer;P. Hasselgren;P. Hasselgren
转录核因子-kappaB (NF-kappaB) 调节大量参与脓毒症和内毒素血症炎症反应的基因。我们最近发现，在内毒素血症期间，空肠粘膜中的 NF-κB 被激活，但胃肠道其他部位的 NF-κB 反应尚不清楚。我们假设在内毒素血症期间，胃肠道不同区域的 NF-κB 被不同程度地激活。通过电泳迁移率变动测定在内毒素血症小鼠和注射盐水小鼠的胃、空肠、回肠和结肠粘膜中测定 NF-kappaB DNA 结合活性。通过蛋白质印迹分析测定 NF-κB 抑制蛋白 IkappaB-α 和 IkappaB-β 的细胞质水平。内毒素血症增加了胃、空肠和回肠粘膜中的 NF-κB 活性，空肠对比胃肠道其他部分更小剂量的内毒素有反应。即使在施用高剂量内毒素后，结肠粘膜中也不会诱导 NF-kappaB DNA 结合活性。注射内毒素的小鼠空肠粘膜中的 IkappaB-α 和 IkappaB-β 水平随着 NF-kappaB 的激活而降低。结果表明，在内毒素血症期间，NF-κB在胃和小肠粘膜中被激活，但在结肠中不被激活，并且空肠对内毒素特别敏感。
The transcription nuclear factor-kappaB (NF-kappaB) regulates a large number of genes involved in the inflammatory response to sepsis and endotoxemia. We recently found that NF-kappaB is activated in the jejunal mucosa during endotoxemia, but the response of NF-kappaB in other parts of the gastrointestinal tract is not known. We hypothesized that NF-kappaB is differentially activated in different regions of the gastrointestinal tract during endotoxemia. NF-kappaB DNA binding activity was determined by electrophoretic mobility shift assay in mucosa of the stomach, jejunum, ileum, and colon from endotoxemic and saline-injected mice. Cytoplasmic levels of the NF-kappaB inhibitory proteins IkappaB-alpha and IkappaB-beta were determined by Western blot analysis. Endotoxemia increased NF-kappaB activity in mucosa of stomach, jejunum, and ileum, with jejunum responding to smaller doses of endotoxin than the other parts of the gastrointestinal tract. NF-kappaB DNA binding activity was not induced in colonic mucosa, even following administration of high doses of endotoxin. IkappaB-alpha and IkappaB-beta levels decreased in jejunal mucosa of endotoxin injected mice, concomitant with activation of NF-kappaB. The results suggest that during endotoxemia, NF-kappaB is activated in mucosa of stomach and small intestine, but not in colon, and that the jejunum is particularly sensitive to endotoxin.