Stimulation of transforming growth factor‐β 1 transcription by cyclosporine

FEBS Letters

Sharma, V.K.¹  Prashar, Y.¹  Sehajpal, P.¹  Suthanthiran, M.¹  Khanna, A.¹ 

[1] The Rogosin Institute, Department of Transplantation and Extracorporeal Therapy, Departments of Medicine, Biochemistry and Surgery, The New York Hospital-Cornell Medical Center, 430 E 71st Street, New York, NY 10021, USA

关键词: Cyclosporine;    TGF-β;    Transcription;    CAT activity;    Mobility shift assay;    Transcription factor;   

DOI  :  10.1016/0014-5793(94)01382-B

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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

【 授权许可】

Unknown