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.
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Authors | Hye-Eun Byeon, Bong-Kyun Park, Joung Han Yim, Hong Kum Lee, Eun-Yi Moon, Dong-Kwon Rhee, Suhkneung Pyo |
Journal | International immunopharmacology
(Int Immunopharmacol)
Vol. 12
Issue 2
Pg. 315-25
(Feb 2012)
ISSN: 1878-1705 [Electronic] Netherlands |
PMID | 22210374
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier B.V. All rights reserved. |
Chemical References |
- Chemokine CCL2
- Depsipeptides
- I-kappa B Proteins
- NF-kappa B
- NFKBIA protein, human
- Nfkbia protein, mouse
- Reactive Oxygen Species
- Tumor Necrosis Factor-alpha
- Vascular Cell Adhesion Molecule-1
- stereocalpin A
- Intercellular Adhesion Molecule-1
- NF-KappaB Inhibitor alpha
- Proto-Oncogene Proteins c-akt
- Extracellular Signal-Regulated MAP Kinases
- p38 Mitogen-Activated Protein Kinases
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Topics |
- Animals
- Cell Adhesion
(drug effects, genetics)
- Cell Survival
(drug effects, genetics)
- Cells, Cultured
- Chemokine CCL2
(genetics, metabolism)
- Depsipeptides
(pharmacology)
- Extracellular Signal-Regulated MAP Kinases
(genetics, metabolism)
- Gene Expression
(drug effects, genetics)
- Human Umbilical Vein Endothelial Cells
(drug effects, metabolism)
- Humans
- I-kappa B Proteins
(genetics, metabolism)
- Intercellular Adhesion Molecule-1
(genetics, metabolism)
- Mice
- Monocytes
(drug effects, metabolism)
- Muscle, Smooth, Vascular
(drug effects, metabolism)
- Myocytes, Smooth Muscle
(drug effects, metabolism)
- NF-KappaB Inhibitor alpha
- NF-kappa B
(genetics, metabolism)
- Phosphorylation
(drug effects, genetics)
- Protein Transport
(drug effects, genetics)
- Proto-Oncogene Proteins c-akt
(genetics, metabolism)
- Reactive Oxygen Species
(metabolism)
- Tumor Necrosis Factor-alpha
(antagonists & inhibitors, genetics, metabolism)
- Vascular Cell Adhesion Molecule-1
(genetics, metabolism)
- p38 Mitogen-Activated Protein Kinases
(genetics, metabolism)
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