Epigallocatechin-3-O-Gallate Inhibits the Angiotensin II-Induced Adhesion Molecule Expression in Human Umbilical Vein Endothelial Cell Via Inhibition of MAPK Pathways

Abstract

Epigallocatechin-3-O-gallate (EGCG) is the main catechin, which is derived from Camellia sinensis plant. Vascular cell adhesion molecules (VCAMs) and intercellular adhesion molecules (ICAMs) mediate the binding of inflammatory cells onto the vascular wall-promoting the early phase of atherosclerosis. In the present study, we investigated the mechanism(s) by which EGCG inhibits angiotensin II (Ang II)-induced elevation of the membrane associated VCAM-1 and ICAM-1 in human umbilical vein endothelial cells (HUVEC). Ang II induced a 40% increase of VCAM-1 and ICAM-1 in the plasma membrane. EGCG (10 to 50 µM) inhibited the effect of Ang II in a concentration-dependent manner. In parallel, the Ang II-induced elevation of the mRNA expressions of VCAM-1 and ICAM-1 in HUVEC were completely inhibited by 50 µM EGCG. Since mitogen-activated protein kinase (MAPK) families are involved in vascular inflammation in response to stressful stimuli, we investigated the effects of EGCG on the MAPK signal transduction pathway stimulated by Ang II. EGCG (30 to 50 µM) completely inhibited the Ang II-induced phosphorylation of ERK (extracellular signal-regulated kinase) 1/2 and p38 MAPK. PD98059, an inhibitor of ERK1/2 inhibited the Ang II-induced increase of VCAM-1 but not of ICAM-1 in the plasma membranes. In contrast, SB203580, an inhibitor of p38 MAPK inhibited both the Ang II-induced enrichment of ICAM-1 and VCAM-1. From these results, it may be concluded that EGCG inhibits the Ang II-induced elevation of VCAM-1 and ICAM-1 in the HUVEC plasma membranes via inhibition of the p38 MAPK and the ERK1/2 signalling pathways resulting in an inhibition of the VCAM-1 and ICAM-1 transcription.

Catechins Inhibit CCL20 Production in IL-17A-Stimulated Human Gingival Fibroblasts

“…We recently reported that EGCG and ECG treatment inhibited p38 MAPK activation in oncostatin M-stimulated HGFs [22]. Moreover, Chae et al reported that EGCG suppressed ERK phosphorylation in angiotensin 2-treated human umbilical vein endothelial cells [23]. Bigelow et al also reported that EGCG and ECG suppressed ERK activation in hepatocyte growth factor-treated tumorigenic breast epithelial cells [24].…”

Luteolin Protects HUVECs from TNF-α-induced Oxidative Stress and Inflammation via its Effects on the Nox4/ROS-NF-κB and MAPK Pathways

“…In the present study, treatment with luteolin was found to inhibit the p38 and ERK1/2 phosphorylation induced by TNF-α. Moreover, the activation of p38 and ERK1/2 has been shown to be associated with the VCAM-1, ICAM-1 and Bcl-2 expression [38][39][40] . This finding was confirmed by our observation that the above three TNF-induced protein expression levels were partly abolished by the inhibitors of p38 and/or ERK1/2.…”

Epigallocatechin-3-Gallate Ameliorates Experimental Autoimmune Encephalomyelitis by Altering Balance among CD4+ T-Cell Subsets

“…First, reduced pathological cells in the periphery are assumed to reduce the frequency of these cells coming across the CNS. Second, EGCG reduces the production or expression of the molecules known to facilitate leukocyte transendothelial migration, such as chemokines IL-8 and monocyte chemoattractant protein-1 [45][46][47] and adhesion molecules 48,49 and to inhibit migration of neutrophils, 50,51 CD8 ϩ T cells, 49 and B cells. 52 Third, the observed EGCG-induced reduction in IFN-␥ and IL-17 production and the proportion of IL-17-IFN-␥ double-positive CD4 ϩ T cells may contribute to the reduced leukocyte infiltration because, as reported, IFN-␥ facilitates Th17 migration across the BBB by enhancing endothelial expression of adhesion molecule ICAM-1, and IL-17 is capable of disrupting the BBB; IL-17-IFN-␥ double-positive cells have a higher capacity for crossing the BBB than either singlepositive cells.…”