This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Murase, T. Articles by Kita, T. Search for Related Content PubMed PubMed Citation Articles by Murase, T. Articles by Kita, T. Related Collections Oxidant stress Pathophysiology Risk Factors Growth factors/cytokines Physiological and pathological control of gene expression

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1412-1420.)
© 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

Takatoshi Murase; Noriaki Kume; Tadashi Hase; Yusuke Shibuya; Yoshinori Nishizawa; Ichiro Tokimitsu; Toru Kita

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

This article has been cited by other articles:

				K. Raina, S. Rajamanickam, G. Deep, M. Singh, R. Agarwal, and C. Agarwal Chemopreventive effects of oral gallic acid feeding on tumor growth and progression in TRAMP mice Mol. Cancer Ther., May 1, 2008; 7(5): 1258 - 1267. [Abstract] [Full Text] [PDF]

				H.-M. Kwon, Y.-J. Choi, J.-S. Choi, S.-W. Kang, J.-Y. Bae, I.-J. Kang, J.-G. Jun, S.-S. Lee, S. S. Lim, and Y.-H. Kang Blockade of Cytokine-Induced Endothelial Cell Adhesion Molecule Expression by Licorice Isoliquiritigenin Through NF-{kappa}B Signal Disruption Experimental Biology and Medicine, February 1, 2007; 232(2): 235 - 245. [Abstract] [Full Text] [PDF]

				E. Waddington, I. B Puddey, and K. D Croft Red wine polyphenolic compounds inhibit atherosclerosis in apolipoprotein E-deficient mice independently of effects on lipid peroxidation Am. J. Clinical Nutrition, January 1, 2004; 79(1): 54 - 61. [Abstract] [Full Text] [PDF]

				J.-W. Chen, Y.-H. Chen, F.-Y. Lin, Y.-L. Chen, and S.-J. Lin Ginkgo biloba Extract Inhibits Tumor Necrosis Factor-{alpha}-Induced Reactive Oxygen Species Generation, Transcription Factor Activation, and Cell Adhesion Molecule Expression in Human Aortic Endothelial Cells Arterioscler. Thromb. Vasc. Biol., September 1, 2003; 23(9): 1559 - 1566. [Abstract] [Full Text] [PDF]

				K. Iijima, M. Yoshizumi, M. Hashimoto, M. Akishita, K. Kozaki, J. Ako, T. Watanabe, Y. Ohike, B. Son, J. Yu, et al. Red Wine Polyphenols Inhibit Vascular Smooth Muscle Cell Migration Through Two Distinct Signaling Pathways Circulation, May 21, 2002; 105(20): 2404 - 2410. [Abstract] [Full Text] [PDF]

				H. Fan, B. Sun, Q. Gu, A. Lafond-Walker, S. Cao, and L. C. Becker Oxygen radicals trigger activation of NF-kappa B and AP-1 and upregulation of ICAM-1 in reperfused canine heart Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1778 - H1786. [Abstract] [Full Text] [PDF]

				F. D'Acquisto, M. J. May, and S. Ghosh Inhibition of Nuclear Factor Kappa B (NF-B):: An Emerging Theme in Anti-Inflammatory Therapies Mol. Interv., February 1, 2002; 2(1): 22 - 35. [Abstract] [Full Text] [PDF]

				D. Giugliano, F. Nappo, L. Coppola, L. Miguel Blanco-Colio, C. Bustos, M. Ortego, M. Angel Hernandez-Presa, P. Cancelas, J. Gomez-Gerique, J. Egido, et al. Pizza and Vegetables Don't Stick to the Endothelium Response Circulation, August 14, 2001; 104 (7): e34 - e35. [Full Text] [PDF]