Hypoxia influences CD40-CD40L mediated inflammation in endothelial and monocytic cells
Hypoxia influences CD40-CD40L mediated inflammation in endothelial and monocytic cells
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DOI：
10.1016/j.imlet.2008.12.010
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发表时间：
2009-02-21
影响因子：
4.4
通讯作者：
Freedman, Jane E.
中科院分区：
文献类型：
--
作者：
Chakrabarti, Subrata;Rizvi, Muhammad;Freedman, Jane E.
CD40与其配体(CD40L)的相互作用参与了动脉粥样硬化的发病过程，并被认为是免疫炎症过程中的中心事件。我们以前的研究表明，CD40-CD40L相互作用调节血小板、中性粒细胞和内皮活性氧物种(ROS)的产生。众所周知，低氧与组织缺血和炎症有关，它还影响ROS的产生，改变细胞的氧化还原状态。然而，低氧对CD40-CD40L介导的血管炎症的影响尚不清楚。我们研究了低氧是否影响CD40-CD40L介导的血管炎症反应、ROS的产生和细胞间的相互作用。我们发现，低氧显著增强CD40L对内皮细胞和单核细胞(THP1)的炎症效应。低氧条件下CD40-CD40L相互作用可诱导细胞产生ROS，合成炎性黏附蛋白细胞间黏附分子1(ICAM1)，并激活应激反应蛋白(p38-MAPK和HSP27)，表明CD40L介导氧化应激的诱导。综上所述，这些数据表明，在低氧条件下，CD40-CD40L的相互作用除了影响信号的变化外，还显著影响黏附分子的表达、应激反应、肌动蛋白聚合和单核细胞与内皮细胞的黏附。综上所述，我们发现缺氧可以改变CD40-CD40L介导的内皮-单核细胞相互作用，在血管炎症和细胞黏附过程中发挥重要作用。(C)2009爱思唯尔B.V.保留所有权利。
The interaction between CD40 and its ligand (CD40L) has been implicated in the pathogenesis of atherosclerosis and is recognized as a central event in the development of immuno-inflammatory processes. Our previous studies have shown that the CD40-CD40L interaction modulates platelet, neutrophil, and endothelial reactive oxygen species (ROS) generation. Hypoxia, known to be associated with tissue ischemia and inflammation, also influences the ROS production and changes the cellular redox state. However, the effect of hypoxia on CD40-CD40L mediated vascular inflammation is unknown. We have investigated whether hypoxia influences CD40-CD40L mediated vascular inflammatory responses, ROS production, and cellular interactions. We found that hypoxia significantly enhances the inflammatory effect of CD40L in both endothelial and monocytic cells (THP1). CD40-CD40L interaction in the presence of hypoxia induces ROS production, the synthesis of an inflammatory adhesive protein intercellular adhesion molecule 1 (ICAM1) and activates stress response proteins (p38 MAP kinase and HSP27), indicating that CD40L mediates the induction of oxidative stress in these cells.Importantly, we found that the effects of CD40L can be transmitted between HUVECs and monocytic THP1 cells through intercellular CD40-CD40L interaction and these processes are augmented under hypoxia. Together, these data indicate that under hypoxic conditions the CD40-CD40L interaction significantly influences adhesion molecule expression, stress generation, actin polymerization, and monocytic adhesion to endothelial cells in addition to changes in signaling. In summary, we show that hypoxia can alter CD40-CD40L mediated endothelial-monocyte interaction, playing a significant role in vascular inflammation and cellular adhesion processes. (C) 2009 Elsevier B.V. All rights reserved.