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

作者：Byeon Hye Eun; Park Bong Kyun; Yim Joung Han; Lee Hong Kum; Moon Eun Yi; Rhee Dong Kwon; Pyo Suhkneung^*

来源：International Immunopharmacology, 2012, 12(2): 315-325.

DOI：10.1016/j.intimp.2011.11.020

• Stereocalpin A
• Inflammation
• Cell adhesion molecule
• ROS
• MAPK
• NF-kappa B
• Akt

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-alpha in vascular smooth muscle cells. Pretreatment of VSMCs for 2 h with stereocalpin A at nontoxic concentrations of 0.1-10 mu g/ml inhibited TNF-alpha-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-alpha-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38, ERK, JNK and Akt. Stereocalpin A also inhibited NK-kappa B activation induced by TNF-alpha. Moreover, stereocalpin A inhibited TNF-alpha-induced I kappa B kinase activation, subsequent degradation of I kappa B alpha, and nuclear translocation of NF-kappa B. Hence, we describe a new anti-inflammatory activity and mechanism of stereocalpin A, owing to the negative regulation of TNF-alpha-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.

• 出版日期2012-2
• 单位中国极地研究中心