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在T细胞中，与人类免疫缺陷病毒增强子的κB元件结合的诱导型核因子可被环孢菌素A以信号依赖的方式阻断。

Inducible nuclear factor binding to the kappa B elements of the human immunodeficiency virus enhancer in T cells can be blocked by cyclosporin A in a signal-dependent manner.

作者信息

Schmidt A, Hennighausen L, Siebenlist U

机构信息

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.

出版信息

J Virol. 1990 Aug;64(8):4037-41. doi: 10.1128/JVI.64.8.4037-4041.1990.

DOI:10.1128/JVI.64.8.4037-4041.1990
PMID:2196387
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC249708/
Abstract

Cyclosporin A (CsA) is thought to exert its immunosuppressive effects by inhibiting the expression of a distinct set of lymphokine genes which are induced upon T-cell activation, among them the gene coding for interleukin-2. In addition, the activation of the human immunodeficiency virus (HIV) is partially suppressed. To better understand the molecular mechanisms underlying suppression by CsA, we have investigated the effects of this drug on transcription factors in T cells. Here we report that the formation of two distinct mitogen-inducible DNA-binding complexes, the kappa B complex within the HIV enhancer and the NFAT-1 complex within the interleukin-2 enhancer, is inhibited in the presence of CsA. The kappa B-binding activity with the HIV enhancer is inhibited only if it is activated via the mitogen phytohemagglutinin whereas phorbol myristate acetate-mediated activation is completely insensitive to the drug. This suggests a model in which functionally indistinguishable kappa B complexes can be activated via two separate pathways of signal transduction distinguishable by CsA.

摘要

环孢素A（CsA）被认为通过抑制一组特定的淋巴因子基因的表达来发挥其免疫抑制作用，这些基因在T细胞活化时被诱导，其中包括编码白细胞介素-2的基因。此外，人类免疫缺陷病毒（HIV）的激活也受到部分抑制。为了更好地理解CsA抑制作用的分子机制，我们研究了这种药物对T细胞中转录因子的影响。在此我们报告，在CsA存在的情况下，两种不同的丝裂原诱导性DNA结合复合物的形成受到抑制，即HIV增强子内的κB复合物和白细胞介素-2增强子内的NFAT-1复合物。只有当HIV增强子的κB结合活性通过丝裂原植物血凝素激活时才会被抑制，而佛波酯肉豆蔻酸酯介导的激活对该药物完全不敏感。这提示了一个模型，即功能上难以区分的κB复合物可以通过两条可被CsA区分的信号转导途径被激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b978/249708/540dffc5f6f0/jvirol00063-0487-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b978/249708/6953b9810ec3/jvirol00063-0486-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b978/249708/c829b6746432/jvirol00063-0486-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b978/249708/540dffc5f6f0/jvirol00063-0487-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b978/249708/6953b9810ec3/jvirol00063-0486-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b978/249708/c829b6746432/jvirol00063-0486-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b978/249708/540dffc5f6f0/jvirol00063-0487-a.jpg

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