THE EFFECT OF IMMUNOSUPPRESSIVE AGENTS ON THE INDUCTION OF NUCLEAR FACTORS THAT BIND TO SITES ON THE INTERLEUKIN-2 PROMOTER

Cyclosporin A (CSA), FK506, and glucocorticosteroids all inhibit the production of lymphokines by decreasing lymphokine gene expression. Previous experiments have defined six different sites that may contribute to the transcriptional control of the interleukin 2 (IL2) promoter, and for each, active nuclear binding factors are induced upon mitogenic stimulation. While dexamethasone markedly blocks the increase in IL2 mRNA in stimulated human blood T cells, we found that the drug does not block the appearance of factors that bind to the transcriptional control sites termed AP-1, AP-3, NF-kB, OCT1, B site, and NF-AT. In contrast, both CSA and FK506 have similar effects : the drugs cause modest decreases in AP-3 and NF-kB, and marked decreases in the activity of AP-1 and NF-AT Therefore, CSA and FK506, while chemically different, seem to act upon a similar pathway that leads to IL2 gene expression, whereas glucocorticoids do not affect this pathway. © 1990, Rockefeller University Press., All rights reserved.