Stimulation of transforming growth factor-beta 1 transcription by cyclosporine.

Overview

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.