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

来源：

FEBS LETTERS | 1995年 / 358卷 / 02期

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

页码：109 / 112

页数：4

共 20 条

[1] BORSON KA, 1991, J IMMUNOL, V147, P3601
[2] BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[3] REGULATION OF THE TRANSFORMING GROWTH-FACTOR-BETA-1 AND FACTOR-BETA-3 PROMOTERS BY TRANSCRIPTION FACTOR SP1
GEISER, AG
BUSAM, KJ
KIM, SJ
LAFYATIS, R
OREILLY, MA
WEBBINK, R
ROBERTS, AB
SPORN, MB
[J]. GENE, 1993, 129 (02) : 223 - 228
[4] LYMPHOKINE AND NONLYMPHOKINE MESSENGER-RNA LEVELS IN STIMULATED HUMAN T-CELLS - KINETICS, MITOGEN REQUIREMENTS, AND EFFECTS OF CYCLOSPORINE-A
GRANELLIPIPERNO, A
ANDRUS, L
STEINMAN, RM
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1986, 163 (04) : 922 - 937
[5] KAHAN BD, 1989, NEW ENGL J MED, V321, P1725
[6] KHANNA A, 1994, TRANSPLANTATION, V57, P577
[7] REGULATION OF TRANSFORMING GROWTH FACTOR-BETA-1 GENE-EXPRESSION BY THE PRODUCT OF THE RETINOBLASTOMA-SUSCEPTIBILITY GENE
KIM, SJ
LEE, HD
ROBBINS, PD
BUSAM, K
SPORN, MB
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (08) : 3052 - 3056
[8] KIM SJ, 1989, J BIOL CHEM, V264, P19373
[9] THE RETINOBLASTOMA GENE-PRODUCT REGULATES SP1-MEDIATED TRANSCRIPTION
KIM, SJ
ONWUTA, US
LEE, YI
LI, R
BOTCHAN, MR
ROBBINS, PD
[J]. MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (06) : 2455 - 2463
[10] KIM SJ, 1989, J BIOL CHEM, V264, P402

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