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Stereocalpin A inhibits the expression of adhesion molecules in activated vascular smooth muscle cells.

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.
AuthorsHye-Eun Byeon, Bong-Kyun Park, Joung Han Yim, Hong Kum Lee, Eun-Yi Moon, Dong-Kwon Rhee, Suhkneung Pyo
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 12 Issue 2 Pg. 315-25 (Feb 2012) ISSN: 1878-1705 [Electronic] Netherlands
PMID22210374 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 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
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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