STIMULATION OF TRANSFORMING GROWTH FACTOR-BETA(1) TRANSCRIPTION BY CYCLOSPORINE

被引:92
|
作者
PRASHAR, Y
KHANNA, A
SEHAJPAL, P
SHARMA, VK
SUTHANTHIRAN, M
机构
[1] CORNELL UNIV,MED CTR,NEW YORK HOSP,ROGOSIN INST,DEPT TRANSPLANTAT & EXTRACORPOREAL THERAPY,NEW YORK,NY 10021
[2] CORNELL UNIV,MED CTR,NEW YORK HOSP,ROGOSIN INST,DEPT MED,NEW YORK,NY 10021
[3] CORNELL UNIV,MED CTR,NEW YORK HOSP,ROGOSIN INST,DEPT BIOCHEM,NEW YORK,NY 10021
[4] CORNELL UNIV,MED CTR,NEW YORK HOSP,ROGOSIN INST,DEPT SURG,NEW YORK,NY 10021
关键词
CYCLOSPORINE; TGF-BETA; TRANSCRIPTION; CAT ACTIVITY; MOBILITY SHIFT ASSAY; TRANSCRIPTION FACTOR;
D O I
10.1016/0014-5793(94)01382-B
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In searching for a candidate mechanism for the inmunosuppressive as,veil 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.
引用
收藏
页码:109 / 112
页数:4
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