Anthocyanin attenuates CD40-mediated endothelial cell activation and apoptosis by inhibiting CD40-induced MAPK activation.
CD40-mediated inflammatory signaling is a potent activator of endothelial cells (ECs) and effective in triggering the pathogenesis of atherosclerosis, a chronic inflammatory disease. Anthocyanin is considered to exert potent cardiovascular-protective effect partially through its anti-inflammatory property, however, the precise mechanism is still unknown. Here we chose cultured human umbilical vein endothelial cells (HUVECs) to explore the influence of anthocyanin on CD40-mediated endothelial activation and apoptosis and the underlying mechanism. Stimulation of human primary HUVECs by CD40 with its physiological ligand CD40L not only augmented MMP-1, -9 secretion and promoted MMP-1, -9 activities, but also induced endothelial cell apoptosis and death. Treatment of ECs with anthocyanins cyanidin-3-O-beta-glucoside (Cy-3-g) and peonidin-3-O-beta-glucoside (Pn-3-g) prevents CD40-induced endothelial activation by inhibiting production of proinflammatory cytokines and matrix metalloproteinases (MMPs). In addition, exposure to anthocyanins inhibits CD40-induced endothelial apoptosis. Anthocyanins also decreased activation of JNK and p38 induced by CD40. Collectively, our findings suggested that the inhibition of JNK and p38 activation interrupts CD40 induced endothelial cell activation and apoptosis, which thereby may represent a mechanism that would explain the anti-inflammatory response of anthocyanin and its athero-protective function.
Xia
Min
M
Department of Nutrition, School of Public Health, Sun Yat-Sen University (Northern Campus) 74 Zhongshan Road 2, Guangzhou 510080, Guangdong Province, PR China.
Ling
Wenhua
W
Zhu
Huilian
H
Ma
Jing
J
Wang
Qing
Q
Hou
Mengjun
M
Tang
Zhihong
Z
Guo
Honghui
H
Liu
Chi
C
Ye
Qingyuan
Q
D000872:Anthocyanins / Q000494:pharmacology*; D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007249:Inflammation; D020935:MAP Kinase Signaling System; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000872:Anthocyanins; D019013:CD40 Antigens; D015815:Cell Adhesion Molecules; D003094:Collagen; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases