© 1999 American Heart Association, Inc.
Vascular Biology |
Gallates Inhibit Cytokine-Induced Nuclear Translocation of NF-
B and Expression of Leukocyte Adhesion Molecules in Vascular Endothelial Cells
From the Biological Science Laboratories, Kao Corp, Ichikaimachi, Tochigi (T.M., T.H., Y.S., Y.N., I.T.), and the Department of Geriatric Medicine, Kyoto University, Kyoto (T.M., N.K., T.K.), Japan.
Correspondence to Noriaki Kume, MD, PhD, Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail nkume{at}kuhp.kyoto-u.ac.jp
Abstract—Gallates (gallic
acid esters) belong to the class of phenolic compounds, which are
abundant in red wine. In this study, we show that gallates can inhibit
cytokine-induced activation of nuclear factor 
B
(NF-B) and thereby reduce expression of
endothelial-leukocyte adhesion molecules in cultured
human umbilical vein endothelial cells (HUVECs).
Pretreatment of HUVECs with ethyl gallate (3 to 10 µmol/L)
significantly suppressed interleukin-1
(IL-1)– or tumor necrosis
factor- (TNF-)– induced mRNA and cell-surface expression of
vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion
molecule 1 (ICAM-1), and E-selectin, which was associated with reduced
adhesion of leukocytes to HUVECs. Gel shift assays with the NF-B
consensus sequence showed the decreased densities of the shifted bands
in gallate-treated HUVECs. Furthermore, gallate pretreatment inhibited
cytokine-induced transcription of a fusion gene, which
consisted of 4 repeats of the NF-B consensus sequence and the
luciferase reporter gene. Immunoblot analysis of
nuclear extracts and whole-cell lysates demonstrated the decreased
amounts of NF-B p65 in nuclei but equal amounts of
inhibitor-B (I-B) in whole-cell lysates
of ethyl gallate–treated HUVECs. Incubation of the nuclear extracts
from cytokine-activated HUVECs with ethyl gallate did
not affect the NF-B shifted bands induced by cytokines in
gel shift assays. Taken together, these data demonstrate that ethyl
gallate can inhibit cytokine-induced nuclear translocation
of NF-B p65 by way of a mechanism independent of I-B
degradation and thereby suppress expression of VCAM-1, ICAM-1, and
E-selectin, which was associated with reduced adhesion of leukocytes.
These results in vitro demonstrate that gallates can exhibit
anti-inflammatory properties by blocking activation of NF-B and
suggest that these natural compounds, abundant in red wine, may play
important roles in the prevention of atherosclerosis
and inflammatory responses in vivo.
Key Words: cell adhesion molecules • transcription factors • atherosclerosis • antioxidant • red wine
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