Regulation of chemokine gene expression in human endothelial cells by proinflammatory cytokines and Borrelia burgdorferi
Regulation of chemokine gene expression in human endothelial cells by proinflammatory cytokines and Borrelia burgdorferi
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DOI：
10.1111/j.1749-6632.1996.tb52953.x
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发表时间：
1996-01-01
期刊：
影响因子：
--
通讯作者：
Shaw, S
中科院分区：
文献类型：
--
作者：
Ebnet, K;Simon, MM;Shaw, S
趋化因子在白细胞向组织募集的过程中起核心作用。通过其趋化活性，它们将白细胞引导至感染/损伤部位。趋化因子已被认为触发白细胞与活化的内皮细胞的牢固粘附以及随后的渗出。对于这些功能，由EC产生的趋化因子特别适合。我们的促炎刺激实验表明，趋化因子诱导EC中的各种刺激，包括炎症细胞因子和细菌结构，如LPS和B的制剂。burgdorferi。所有这些试剂对趋化因子的诱导发生迅速，并且不需要新的蛋白质合成。两种趋化因子MCP-1和IL-8对非常低剂量（0.1- 1U/ml）的促炎细胞因子有反应，这在可溶性炎症介质可能仍然有限时免疫应答开始时是重要的。趋化因子RANTES、IP-10和mig显示出由低剂量（1U/ml）的几种炎性介质的协同诱导，这在仅存在有限量的炎性刺激时再次是重要的。B上调EC和成纤维细胞两种细胞类型中的六种趋化因子基因以及编码粘附分子的基因。burgdorferi认为趋化因子可能在螺旋体诱导的炎症反应和随后的免疫反应的调节中发挥核心作用。最近的证据表明，具有致病潜力的T细胞有助于莱姆病晚期的慢性炎症。因此，使用阻断趋化因子活性的治疗剂可能有助于治疗慢性莱姆关节炎。
Chemokines play a central role in the process of leukocyte recruitment to tissues. By their chemotactic activity they guide leukocytes to the site of infection/injury. Chemokines have been suggested to trigger firm adhesion of leukocytes to activated endothelial cells as well as the subsequent diapedesis. For these functions, chemokines produced by EC are particularly well suited. Our experiments with proinflammatory stimuli demonstrate that chemokines are induced in EC by a variety of stimuli including inflammatory cytokines and bacterial structures such as LPS and preparations of B. burgdorferi. The induction of chemokines by all of these agents occurs rapidly and does not require new protein synthesis. Two chemokines, MCP-1 and IL-8, respond to very low doses (0.1-1 U/ml) of proinflammatory cytokines which is important at the beginning of an immune response when soluble inflammatory mediators might still be limiting. The chemokines RANTES, IP-10, and mig show synergistic induction by low doses (1 U/ml) of several inflammatory mediators, which again is important when only limiting amounts of inflammatory stimuli are present. The upregulation of six chemokine genes as well as genes encoding adhesion molecules in two cell types, EC and fibroblasts, by B. burgdorferi suggests that chemokines might play a central role in the regulation of spirochete-induced inflammatory responses and the subsequent immune responses. Recent evidence suggests that T cells with pathogenic potential contribute to chronic inflammation at the late stage of Lyme disease. Therefore, the use of therapeutic agents that block chemokine activity might be useful in treating chronic Lyme arthritis.