CYCLOSPORINE-A SPECIFICALLY INHIBITS FUNCTION OF NUCLEAR PROTEINS INVOLVED IN T-CELL ACTIVATION
CYCLOSPORINE-A SPECIFICALLY INHIBITS FUNCTION OF NUCLEAR PROTEINS INVOLVED IN T-CELL ACTIVATION
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DOI：
10.1126/science.2595372
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发表时间：
1989-12-22
期刊：
影响因子：
56.9
通讯作者：
CRABTREE, GR
中科院分区：
文献类型：
--
作者：
EMMEL, EA;VERWEIJ, CL;CRABTREE, GR
环孢菌素A的一个作用被认为是其许多免疫抑制作用的核心，是其抑制T淋巴细胞活化的早期事件的能力，例如响应于抗原受体起始的信号的淋巴因子基因转录。发现环孢菌素A特异性地抑制NF-AT、AP-3的DNA结合活性的出现，并且在较小程度上抑制NF-κ的DNA结合活性的出现。B，在白细胞介素-2及其受体以及其他几种淋巴因子的基因转录激活中似乎很重要的核蛋白。此外，环孢菌素A废除的NF-AT结合位点的能力，激活一个连接的启动子在转染的有丝分裂原刺激的T淋巴细胞和转基因小鼠的淋巴细胞。这些结果表明，环孢菌素A要么直接抑制T淋巴细胞活化的关键核蛋白的功能，要么抑制从抗原受体到细胞核的信号传递级联的更近端成员的作用。
One action of cyclosporin A thought to be central to many of its immunosuppressive effects is its ability to inhibit the early events of T lymphocyte activation such as lymphokine gene transcription in response to signals initiated at the antigen receptor. Cyclosporin A was found to specifically inhibit the appearance of DNA binding activity of NF-AT, AP-3, and to a lesser extent NF-.kappa. B, nuclear proteins that appear to be important in the transcriptional activation of the genes for interleukin-2 and its receptor, as well as several other lymphokines. In addition, cyclosporin A abolished the ability of the NF-AT binding site to activate a linked promoter in transfected mitogen-stimulated T lymphocytes and in lymphocytes from transgenic mice. These results indicate that cyclosporin A either directly inhibits the function of nuclear proteins critical to T lymphocyte activation or inhibits the action of a more proximal member of the signal transmission cascade leading from the antigen receptor to the nucleus.