The immunosuppressives FK 506 and cyclosporin A inhibit the generation of protein factors binding to the two purine boxes of the interleukin 2 enhancer.
Like Cyclosporin A (CsA), the macrolide FK 506 is a potent immunosuppressive that inhibits early steps of T cell activation, including the synthesis of Interleukin 2 (II-2) and numerous other lymphokines. The block of II-2 synthesis occurs at the transcriptional level. At concentrations that block T cell activation, FK 506 and CsA inhibit the proto-enhancer activity of Purine boxes of the II-2 promoter and the generation of lymphocyte-specific factors binding to the Purine boxes. Under the same conditions, the DNA binding of other II-2 enhancer factors remains unaffected by both compounds. These results support the view that FK 506 and CsA, which both inhibit the activity of peptidylprolyl cis/trans isomerases, suppress T cell activation by a similar, if not identical mechanism.
Brabletz
T
T
Institut für Virologie und Immunbiologie, Universität Würzburg, FRG.
Pietrowski
I
I
Serfling
E
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects; D001483:Base Sequence; D003524:Cyclosporins / Q000494:pharmacology*; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011687:Purines / Q000378:metabolism; D016559:Tacrolimus; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D003524:Cyclosporins; D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011687:Purines; D004247:DNA; D016559:Tacrolimus