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Regulation of granulocyte-macrophage colony-stimulating factor and E-
selectin expression in endothelial cells by cyclosporin A and the T- cell
transcription factor NFAT
GW Cockerill, AG Bert, GR Ryan, JR Gamble, MA Vadas and PN Cockerill
Division of Human Immunology, Hanson Centre For Cancer Research, Adelaide,
Australia.
Nuclear factor of activated T cells (NFAT) was originally described as a
T-cell-specific transcription factor athat supported the activation of
cytokine gene expression and mediated the immunoregulatory effects of
cyclosporin A (CsA). As we observed that activated endothelial cells also
expressed NFAT, we tested the antiinflammatory properties of CsA in
endothelial cells. Significantly, CsA completely suppressed the induction
of NFAT in endothelial cells and inhibited the activity of
granulocyte-macrophage colony-stimulating factor (GM-CSF) gene regulatory
elements that use NFAT by 60%. CsA similarly mediated a reduction of up to
65% in GM-CSF mRNA and protein expression in activated endothelial cells.
CsA also suppressed E-selectin, but not vascular cell adhesion molecule-1
(VCAM-1) expression in endothelial cells, even though the E-selectin
promoter is activated by NF-kappa B rather than NFAT. Hence, induction of
cell surface expression of this leukocyte adhesion molecule by tumor
necrosis factor (TNF)-alpha was reduced by 40% in the presence of CsA, and
this was reflected by a 29% decrease in neutrophil adhesion. The effects of
CsA on endothelial cells were also detected at the chromatin structure
level, as DNasel hypersensitive sites within both the GM-CSF enhancer and
the E-selectin promoter were suppressed by CsA. This represents the first
report of NFAT in endothelial cells and suggests mechanisms by which CsA
could function as an antiinflammatory agent.
Volume 86,
Issue 7,
pp. 2689-2698,
10/01/1995
Copyright © 1995 by The American Society of Hematology
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|
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|
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|
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|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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190(2):
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[Abstract]
[Full Text]
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|
|
|
|
|
|
|
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[Full Text]
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|
|
|
|
|
|
|
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19(3):
2032 - 2043.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Aoki, G. Zhao, D. Qiu, L. Shi, and P. N. Kao
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275(6):
L1164 - L1172.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-I. Lee and G. J. Burckart
Nuclear Factor Kappa B: Important Transcription Factor and Therapeutic Target
J. Clin. Pharmacol.,
November 1, 1998;
38(11):
981 - 993.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K. L. Abbott, B. B. Friday, D. Thaloor, T.J. Murphy, and G. K. Pavlath
Activation and Cellular Localization of the Cyclosporine A-sensitive Transcription Factor NF-AT in Skeletal Muscle Cells
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October 1, 1998;
9(10):
2905 - 2916.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
F. J. Garcia-Cozar, H. Okamura, J. F. Aramburu, K. T. Y. Shaw, L. Pelletier, R. Showalter, E. Villafranca, and A. Rao
Two-site Interaction of Nuclear Factor of Activated T Cells with Activated Calcineurin
J. Biol. Chem.,
September 11, 1998;
273(37):
23877 - 23883.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Boss, X. Wang, L. F. Koppelman, K. Xu, and T. J. Murphy
Histamine Induces Nuclear Factor of Activated T Cell-Mediated Transcription and Cyclosporin A-Sensitive Interleukin-8 mRNA Expression in Human Umbilical Vein Endothelial Cells
Mol. Pharmacol.,
August 1, 1998;
54(2):
264 - 272.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
V. Boss, K. L. Abbott, X.-F. Wang, G. K. Pavlath, and T. J. Murphy
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J. Biol. Chem.,
July 31, 1998;
273(31):
19664 - 19671.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Huang, M. Ding, J. Li, S. S. Leonard, Y. Rojanasakul, V. Castranova, V. Vallyathan, G. Ju, and X. Shi
Vanadium-induced Nuclear Factor of Activated T Cells Activation through Hydrogen Peroxide
J. Biol. Chem.,
June 15, 2001;
276(25):
22397 - 22403.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. G. Loots, I. Ovcharenko, L. Pachter, I. Dubchak, and E. M. Rubin
rVista for Comparative Sequence-Based Discovery of Functional Transcription Factor Binding Sites
Genome Res.,
May 1, 2002;
12(5):
832 - 839.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
