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Cyclosporin A and FK506 prevent the derepression of the IL-2 gene in mitogen-induced primary T lymphocytes.
Journal article

Cyclosporin A and FK506 prevent the derepression of the IL-2 gene in mitogen-induced primary T lymphocytes.

  • 1992-03-01
Published in:
  • Cytokine. - 1992
Animals
Cells, Cultured
Cyclosporine
DNA-Binding Proteins
Interleukin-2
Lymphocyte Activation
Mitogens
Oocytes
Promoter Regions, Genetic
Repressor Proteins
T-Lymphocytes
Tacrolimus
Transcription Factors
Transcription, Genetic
Xenopus
English In resting primary T lymphocytes the interleukin 2 (IL-2) gene is silenced by a repressor binding to the Pud element spanning positions -292 to -264 upstream of the cap site. Upon T-cell activation, this silencer is displaced by a positive transcription factor (TF) and the gene is derepressed and transcribed. Cyclosporin A (CsA) and FK506 interfere with normal derepression of the IL-2 gene. Both drugs exert no direct effect on basal transcription of the IL-2 or control viral genes. Direct addition does not abolish the active state of positive TFs present in proteins from activated T cells. However, if T cells are activated in the presence of either drug, their proteins not only fail to derepress, but efficiently and irreversibly silence IL-2 transcription. DNA-protein binding data show that proteins present in drug-treated cells form retarded complexes corresponding in size to the silencer and positive TF. Thus, in drug-treated cells a functional silencer persists, and a positive TF-like factor appears which is functionally abnormal. Moreover, drug-treated T cells appear to form a component that prevents functioning of normal positive TF.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/82838
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