Stimulation of transforming growth factor-beta 1 transcription by cyclosporine

FEBS Lett. 1995 Jan 23;358(2):109-12. doi: 10.1016/0014-5793(94)01382-b.


In searching for a candidate mechanism for the immunosuppressive as well as fibrogenic consequences of cyclosporine usage, we have explored the hypothesis that cyclosporine stimulates transcription of transforming growth factor-beta 1 (TGF-beta 1), a multifunctional cytokine endowed with immunosuppressive and fibrogenic properties. Our results demonstrate that cyclosporine (i) stimulates TGF-beta 1 promoter-dependent transcription of chloramphenicol acetyl transferase gene in transiently transfected human A-549 cells, (ii) stimulates the synthesis of TGF-beta 1 RNA transcripts in human T cells, and (iii) permits the expression/emergence of DNA regulatory proteins (retinoblastoma control factor-1 (RCF-1) and RCF-2) that bind and regulate TGF-beta 1 promoter activity. Our studies demonstrate for the first time that cyclosporine stimulates TGF-beta 1 gene transcription and suggest a novel mechanism of action of cyclosporine.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cell Line
  • Cyclosporine / pharmacology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Promoter Regions, Genetic
  • T-Lymphocytes / metabolism
  • Transcription, Genetic / drug effects*
  • Transforming Growth Factor beta / genetics*


  • DNA-Binding Proteins
  • Oligodeoxyribonucleotides
  • Transforming Growth Factor beta
  • Cyclosporine