© 1997 American Heart Association, Inc.
Articles |
Inhibition of Tissue Factor Gene Activation in Cultured Endothelial Cells by Curcumin
Suppression of Activation of Transcription Factors Egr-1, AP-1, and NF-
B
From the Departments of Medical Specialties and Biochemistry, The University of Texas Health Center at Tyler, Texas.
Correspondence to Usha R. Pendurthi, PhD, Department of Medical Specialties, UT Health Center at Tyler, Tyler, TX 75710. E-mail usha{at}uthct.edu
Abstract Binding of plasma factor VII(a) to tissue factor
(TF) initiates the coagulation cascade. In health, TF is not expressed
in endothelial cells. However,
endothelial cells express TF in response to
lipopolysaccharide (LPS), tumor necrosis factor-
(TNF),
and other biological stimuli. TF expression by
endothelial cells is implicated in thrombotic disorders
in patients with a variety of clinical disorders. In the present
study, we demonstrate that curcumin (diferulolylmethane), a known
anticarcinogenic and anti-inflammatory agent, inhibited phorbol
12-myristate 13-acetate (PMA), LPS, TNF, and
thrombin-induced TF activity and TF gene transcription in human
endothelial cells. The present data show that
curcumin prevented the activation of c-Rel/p65, which is essential for
TF gene activation in endothelial cells, by impairing
the proteolytic degradation inhibitor protein, IB.
The data also show that curcumin downregulated AP-1 binding activity.
The present studies are the first to demonstrate that PMA, but not
LPS, TNF, and thrombin, induced Egr-1 binding to the second
serum-responsive region (SRR-2) of TF promoter and that curcumin
inhibited the PMA-induced Egr-1 binding to SRR-2. Overall, the data
suggest that the anticarcinogenic and anti-inflammatory properties of
curcumin may be related to its ability to inhibit cellular gene
expression regulated by transcription factors NF-B, AP-1, and
Egr-1.
Key Words: tissue factor • transcription factors • endothelium • curcumin
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