Cyclosporin A interferes with the inducible degradation of NF-kappa B inhibitors, but not with the processing of p105/NF-kappa B1 in T cells

Eur J Immunol. 1997 Jul;27(7):1601-9. doi: 10.1002/eji.1830270703.


The transcription factor NF-kappa B controls the induction of numerous cytokine promoters during the activation of T lymphocytes. Inhibition of T cell activation by the immunosuppressants cyclosporin A (CsA) and FK506 exerts a suppressive effect on the induction of these NF-kappa B-controlled cytokine promoters. We show for human Jurkat T leukemia cells, as well as human and mouse primary T lymphocytes, that this inhibitory effect is accompanied by an impaired nuclear translocation of the Rel proteins c-Rel, RelA/p65 and NF-kappa B1/p50, whereas the nuclear appearance of RelB remains unaffected. CsA does not interfere with the synthesis of Rel proteins, but prevents the inducible degradation of cytosolic NF-kappa B inhibitors I kappa B alpha and I kappa B beta upon T cell activation. CsA neither inhibits the processing of the NF-kappa B1 precursor p105 to p50, nor does it "stabilize" the C-terminal portion of p105, I kappa B gamma, which is degraded during p105 processing to mature p50. These results indicate that CsA interferes with a specific event in the signal-induced degradation of I kappa B alpha and I kappa B beta, but does not affect the processing of NF-kappa B1/p105 to p50.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport / genetics
  • Biological Transport / immunology
  • Cell Nucleus / genetics
  • Cell Nucleus / immunology
  • Cyclosporine / pharmacology*
  • Cysteine Endopeptidases / drug effects
  • Cysteine Endopeptidases / metabolism
  • Dose-Response Relationship, Immunologic
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Multienzyme Complexes / drug effects
  • Multienzyme Complexes / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / drug effects*
  • NF-kappa B / metabolism
  • NF-kappa B p50 Subunit
  • Proteasome Endopeptidase Complex
  • Protein Precursors / drug effects*
  • Protein Precursors / metabolism
  • Protein Processing, Post-Translational / drug effects*
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / drug effects*
  • Proto-Oncogene Proteins / metabolism
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tacrolimus / pharmacology
  • Transcription Factor RelB
  • Transcription Factors*


  • Multienzyme Complexes
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Protein Precursors
  • Proto-Oncogene Proteins
  • RELB protein, human
  • Relb protein, mouse
  • Transcription Factors
  • Transcription Factor RelB
  • Cyclosporine
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Tacrolimus