| Abstract: |
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-KB, 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 hi 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. |
| Keywords: |
mutation; t-lymphocytes; nuclear protein; cell line; transcription, genetic; mus musculus; nuclear proteins; gene expression regulation; lymphocyte activation; molecular sequence data; cell culture; base sequence; cyclosporin a; chromosome deletion; repetitive sequences, nucleic acid; t lymphocyte activation; interleukin-2; receptors, interleukin-2; enhancer elements (genetics); cyclosporins; oligonucleotide probes; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; genes, structural
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