Abstract
Up-regulation of cell adhesion molecules on vascular smooth muscle cells (VSMCs) and leukocyte recruitment to the vascular wall contribute to vascular inflammation and atherosclerosis. Stereocalpin A, a chemical compound of the Antarctic lichen Ramalina terebarata, displays tumoricidal activity against several different tumor cell types. However, other biological activities of stereocalpin A and its molecular mechanisms remain unknown. In this study, our work is directed toward studying the in vitro effects of stereocalpin A on the ability to suppress the expression of adhesion molecules induced by TNF-α in vascular smooth muscle cells. Pretreatment of VSMCs for 2h with stereocalpin A at nontoxic concentrations of 0.1-10 μg/ml inhibited TNF-α-induced adhesion of THP-1 monocytic cells and expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Stereocalpin A reduced TNF-α-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38, ERK, JNK and Akt. Stereocalpin A also inhibited NK-κB activation induced by TNF-α. Moreover, stereocalpin A inhibited TNF-α-induced ΙκΒ kinase activation, subsequent degradation of ΙκΒα, and nuclear translocation of NF-κB. Hence, we describe a new anti-inflammatory activity and mechanism of stereocalpin A, owing to the negative regulation of TNF-α-induced adhesion molecule and MCP-1 expression, monocyte adhesion and ROS production in vascular smooth muscle cells. These results suggest that stereocalpin A has the potential to exert a protective effect by modulating inflammation within the atherosclerotic lesion.
Copyright © 2011 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Adhesion / drug effects
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Cell Adhesion / genetics
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Cell Survival / drug effects
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Cell Survival / genetics
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Cells, Cultured
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Chemokine CCL2 / genetics
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Chemokine CCL2 / metabolism
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Depsipeptides / pharmacology*
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Extracellular Signal-Regulated MAP Kinases / genetics
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Expression / drug effects
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Gene Expression / genetics
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Human Umbilical Vein Endothelial Cells / drug effects
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Human Umbilical Vein Endothelial Cells / metabolism
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Humans
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I-kappa B Proteins / genetics
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I-kappa B Proteins / metabolism
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Intercellular Adhesion Molecule-1 / genetics*
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Intercellular Adhesion Molecule-1 / metabolism*
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Mice
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Monocytes / drug effects
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Monocytes / metabolism
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Muscle, Smooth, Vascular / drug effects*
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Muscle, Smooth, Vascular / metabolism
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Myocytes, Smooth Muscle / drug effects*
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Myocytes, Smooth Muscle / metabolism
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NF-KappaB Inhibitor alpha
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Phosphorylation / drug effects
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Phosphorylation / genetics
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Protein Transport / drug effects
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Protein Transport / genetics
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Reactive Oxygen Species / metabolism
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
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Vascular Cell Adhesion Molecule-1 / genetics*
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Vascular Cell Adhesion Molecule-1 / metabolism*
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p38 Mitogen-Activated Protein Kinases / genetics
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Chemokine CCL2
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Depsipeptides
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I-kappa B Proteins
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NF-kappa B
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NFKBIA protein, human
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Nfkbia protein, mouse
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Reactive Oxygen Species
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Tumor Necrosis Factor-alpha
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Vascular Cell Adhesion Molecule-1
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stereocalpin A
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Intercellular Adhesion Molecule-1
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NF-KappaB Inhibitor alpha
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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p38 Mitogen-Activated Protein Kinases