Premium
S ‐Allyl‐ L ‐Cysteine Sulfoxide Inhibits Tumor Necrosis Factor‐Alpha Induced Monocyte Adhesion and Intercellular Cell Adhesion Molecule‐1 Expression in Human Umbilical Vein Endothelial Cells
Author(s) -
Hui Chai,
Like Wo,
Yan Fu,
Tian Xie,
Qiuyan Wang,
Lifeng Huang
Publication year - 2010
Publication title -
the anatomical record: advances in integrative anatomy and evolutionary biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.21070
Subject(s) - cell adhesion molecule , intercellular adhesion molecule 1 , microbiology and biotechnology , tumor necrosis factor alpha , cell adhesion , umbilical vein , chemistry , monocyte , proinflammatory cytokine , biochemistry , biology , inflammation , cell , immunology , in vitro
Garlic and its water‐soluble allyl sulfur‐containing compound, S ‐Allyl‐ L ‐cysteine Sulfoxide (ACSO), have shown antioxidant and anti‐inflammatory activities, inhibiting the development of atherosclerosis. However, little is known about the mechanism(s) underlying the therapeutic effect of ACSO in inhibiting the formation of atherosclerostic lesion. This study aimed to investigate whether ACSO could modulate tumor necrosis factor‐alpha (TNF‐α)‐induced expression of intercellular cell adhesion molecule‐1, monocyte adhesion and TNF‐α‐mediated signaling in human umbilical vein endothelial cells. While TNF‐α promoted the intercellular cell adhesion molecule‐1 mRNA transcription in a dose‐ and time‐dependent manner, ACSO treatment significantly reduced the levels of TNF‐α‐induced intercellular cell adhesion molecule‐1 mRNA transcripts ( P < 0.01). Furthermore, ACSO dramatically inhibited TNF‐α triggered adhesion of THP‐1 monocytes to endothelial cells and porcine coronary artery rings. Moreover, ACSO mitigated TNF‐α induced depolarization of mitochondrial membrane potential and overproduction of superoxide anion, associated with the inhibition of NOX4, a subunit of nicotinamide adenine dinucleotide phosphate‐oxidase, mRNA transcription. In addition, ACSO also inhibited TNF‐α‐induced phosphorylation of JNK, ERK1/2 and IκB, but not p38. Apparently, ACSO inhibited proinflammatory cytokine‐induced adhesion of monocytes to endothelial cells by inhibiting the mitogen‐activated protein kinase signaling and related intercellular cell adhesion molecule‐1 expression, maintaining mitochondrial membrane potential, and suppressing the overproduction of superoxide anion in endothelial cells. Therefore, our findings may provide new insights into ACSO on controlling TNF‐α‐mediated inflammation and vascular disease. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.