The role of endothelial interleukin‐8/NADPH oxidase 1 axis in sepsis
The role of endothelial interleukin‐8/NADPH oxidase 1 axis in sepsis
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DOI：
10.1111/j.1365-2567.2010.03303.x
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发表时间：
2010-11
期刊：
影响因子：
6.4
通讯作者：
Takashi Miyoshi;K. Yamashita;T. Arai;Kokichi Yamamoto;K. Mizugishi;T. Uchiyama
中科院分区：
文献类型：
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作者：
Takashi Miyoshi;K. Yamashita;T. Arai;Kokichi Yamamoto;K. Mizugishi;T. Uchiyama
脓毒症是一种全身性炎症性疾病，由宿主的高炎症反应引起，而不是由入侵的生物体引起。内皮细胞在脓毒症的发病中起着至关重要的作用。在这项研究中，我们研究了白细胞介素- 8 (IL - 8)，一种已知的中性粒细胞化学引诱剂，对脂多糖（LPS）诱导的内皮细胞产生活性氧（ROS）的影响，及其在LPS介导的脓毒症发病机制中的意义。结果表明，IL‐8直接诱导人脐静脉内皮细胞（HUVECs）产生ROS，并介导LPS诱导的HUVECs产生ROS。LPS刺激huvec强烈增强组织因子表达，这是严重脓毒症的标志，可被IL - 8敲低抑制。我们进一步发现，在LPS刺激的HUVECs中，NADPH氧化酶（Nox） 1的表达被IL - 8敲低明显抑制，而Nox1敲低则降低了组织因子的表达，这表明内皮细胞中的LPS/IL - 8信号主要由Nox1介导。综上所述，LPS刺激内皮细胞导致IL - 8-Nox1轴的激活，增强ROS的产生，最终导致严重脓毒症的进展。
Sepsis is a generalized inflammatory disease, caused by the hyperinflammatory response of the host, rather than by invading organisms. Endothelial cells play a crucial role in the pathogenesis of sepsis. In this study, we investigated the effects of interleukin‐8 (IL‐8), a known neutrophil chemoattractant, on lipopolysaccharide (LPS) ‐induced reactive oxygen species (ROS) production by endothelial cells, and its significance in the pathogenesis of LPS‐mediated sepsis. The results revealed that IL‐8 directly induced ROS production in human umbilical vein endothelial cells (HUVECs), and also mediated LPS‐induced ROS production by HUVECs. Stimulation of HUVECs by LPS strongly enhanced tissue factor expression, a hallmark of severe sepsis, which was suppressed by IL‐8 knockdown. We further discovered that NADPH oxidase (Nox) 1 expression in LPS‐stimulated HUVECs was markedly repressed by IL‐8 knockdown, and Nox1 knockdown reduced tissue factor expression, suggesting that the LPS/IL‐8 signalling in endothelial cells was predominantly mediated by Nox1. In conclusion, LPS stimulation of endothelial cells causes activation of the IL‐8–Nox1 axis, enhances the production of ROS, and ultimately contributes to the progression of severe sepsis.