Stimulation of transforming growth factor- beta sub(1) transcription by cyclosporine

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 sub(2) (TGF- beta sub(1)), a multifunctional cytokine endowed with immunosuppressive and fibrogenic properties. Our results demonstrate that cyclosporine (i) stimulates TGF- beta sub(1) promoter-dependent transcription of chloramphenicol acetyl transferase gene in transiently transfected human A-549 cells, (ii) stimulates the synthesis of TGF- beta sub(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 sub(1) promoter activity. Our studies demonstrate for the first time that cyclosporine stimulates TGF- beta sub(1) gene transcription and suggest a novel mechanism of action of cyclosporine.