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首页> 外文期刊>International immunopharmacology >mTOR-inhibitors simultaneously inhibit proliferation and basal IL-6 synthesis of human coronary artery endothelial cells.
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mTOR-inhibitors simultaneously inhibit proliferation and basal IL-6 synthesis of human coronary artery endothelial cells.

机译：mTOR抑制剂同时抑制人冠状动脉内皮细胞的增殖和基础IL-6合成。

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Divergent results regarding the immunosuppressive effects of mammalian-target-of-rapamycin-(mTOR)-inhibitors on venous endothelial cells (ECs) have highlighted the importance of an accurate EC-model. The purpose of this study was to determine mTOR-inhibitor effects at a specific site of action -- the human coronary-artery-ECs (HCAECs) -- and to compare these data with results gained from cultures of human saphenous vein ECs (HSVECs). This EC-model could enable us to gain insight into site-specific pharmacodynamics and the immunosuppressive management of transplant vasculopathy. ECs were cultivated with rising concentrations of mTOR-inhibitors in the presence/absence of tumor necrosis factor (TNF). Cell counts, DNA-synthesis, cytotoxicity and concentrations of the cytokine IL-6 as well as the chemokines IL-8 and MCP-1 were measured. Half-maximal inhibitory effects on cell growth were reached after about 30 h incubation and both cell types showed equal responses regarding cell growth and DNA-synthesis after 48 h incubation time. mTOR-inhibitors failed to suppress basal/TNF-induced secretion of IL-8 and MCP-1, but IL-6 synthesis after TNF-induction was reduced to 35%. In contrast to human saphenous vein ECs (HSVECs), mTOR-inhibitors also reduced basal IL-6-secretion of HCAECs (to 55%) and cell proliferation was simultaneously inhibited within the same concentration range. Taking everything into account, we conclude that EC-proliferation is inhibited at concentrations needed to suppress TNF-stimulated IL-6 synthesis. Furthermore, the specific suppression of basal arterial IL-6-secretion and the delayed onset of the mTOR-inhibitor effect on HCAEC-proliferation (maximum reached after about 36 h) might be of relevance for the prevention of transplant vasculopathy at its initial stage, e.g. as a component of cardioplegic solutions.
机译：关于哺乳动物雷帕霉素靶标（mTOR）抑制剂对静脉内皮细胞（ECs）的免疫抑制作用的不同结果强调了精确EC模型的重要性。这项研究的目的是确定mTOR抑制剂在特定作用部位-人类冠状动脉EC（HCAEC）的作用-并将这些数据与人类隐静脉EC（HSVEC）培养的结果进行比较。这种EC模型可以使我们深入了解特定部位的药效学和移植血管病的免疫抑制治疗。在存在/不存在肿瘤坏死因子（TNF）的情况下，用浓度升高的mTOR抑制剂培养EC。测量细胞因子IL-6以及趋化因子IL-8和MCP-1的细胞计数，DNA合成，细胞毒性和浓度。孵育约30 h后达到对细胞生长的一半最大抑制作用，孵育48 h后两种细胞类型均显示出对细胞生长和DNA合成的相同反应。 mTOR抑制剂无法抑制基础/ TNF诱导的IL-8和MCP-1分泌，但TNF诱导后IL-6的合成减少到35％。与人大隐静脉EC（HSVEC）相比，mTOR抑制剂还降低了HCAEC的基础IL-6分泌（至55％），并且在相同浓度范围内同时抑制了细胞增殖。考虑到所有因素，我们得出结论，在抑制TNF刺激的IL-6合成所需的浓度下，EC增殖受到抑制。此外，基底动脉IL-6分泌的特异性抑制和mTOR抑制剂对HCAEC增殖的延迟发作效应（在约36 h后达到最大）可能与在其初始阶段预防移植血管病变有关，例如作为心脏停搏液的组成部分。

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