Cyclosporine downregulates Fas ligand expression on vascular endothelial cells: implication for accelerated vasculopathy by immunosuppressive therapy.
Cyclosporine downregulates Fas ligand expression on vascular endothelial cells: implication for accelerated vasculopathy by immunosuppressive therapy.
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环孢素下调血管内皮细胞上的 Fas 配体表达：免疫抑制治疗加速血管病变的意义。
DOI：
10.1006/bbrc.1999.1392
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Walsh,K
中科院分区：
文献类型：
--
作者：
Sata,M;Walsh,K
尽管采用环孢素 A (CyA) 和 FK506 进行免疫抑制治疗已显着提高了器官移植受者的早期生存率，但这些免疫抑制剂的使用与移植动脉硬化的高发生率相关。移植相关的动脉硬化被认为是由受体对同种异体移植物的炎症反应引起的，因为其特征是移植血管的早期单核细胞浸润。我们报道血管内皮细胞天然表达死亡因子Fas配体，其可能起到抑制有害白细胞浸润的作用。在这里，我们发现 CyA 或 FK506 下调内皮细胞上的 FasL 表达，同时降低对 Fas 承载细胞的细胞毒性。我们的研究结果不仅证明了这些药物的新颖生物学作用，而且还提出了免疫抑制治疗导致动脉粥样硬化形成的机制。
Although the introduction of cyclosporine A (CyA) and FK506 for immunosuppressive therapy has dramatically enhanced the early survival of organ transplant recipients, administration of these immunosuppresants is correlated with high incidence of transplant arteriosclerosis. Transplant-associated arteriosclerosis is believed to result from recipient inflammatory responses to the allograft, as it is characterized by early mononuclear cell infiltration of the transplanted vessel. We reported that vascular endothelial cells naturally express a death factor, Fas ligand, that may function to inhibit detrimental leukocyte infiltration. Here, we show that CyA or FK506 downregulates FasL expression on endothelial cells with accompanying decrease in the cytotoxicity toward Fas-bearing cells. Our findings not only demonstrate a novel biological action of these drugs, but also suggest a mechanism by which immunosupressive treatment contributes to atherogenesis.