Regulation of adhesion molecules expression in TNF-α-stimulated brain microvascular endothelial cells by tanshinone IIA: involvement of NF-κB and ROS generation.
Pro-inflammatory cytokine-mediated expression of cell surface adhesion molecules plays a key role in endothelial cell injury, leading to vascular inflammation and the development of many cerebrovascular diseases. Thus, antiinflammatory agents targeting these adhesion molecules may represent potential drugs for the prevention and treatment of cerebrovascular diseases. The present study explored the effects of tanshinone IIA (Tan IIA), an active ingredient present in the Salvia miltiorrhiza root, on the expression of cellular adhesion molecules in TNF-α-stimulated brain microvascular endothelial cells (BMVECs). Treatment with Tan IIA was found to suppress the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), resulting in inhibition of TNF-α-induced adhesion of neutrophils to BMVECs in a dose-dependent manner. In addition, Tan IIA significantly inhibited TNF-α-induced production of reactive oxygen species (ROS), which was accompanied by decreased malondialdehyde (MDA) levels. Treatment with Tan IIA also inhibited nuclear factor-kappa B (NF-κB) activation. Together, these results suggest that Tan IIA regulates TNF-α-induced expression of VCAM-1 and ICAM-1 through inhibition of NF-κB activation and ROS generation in BMVECs.
Tang
Chao
C
Department of Neurosurgery, The General Hospital of Shenyang Military Region, Shenyang 110016, Liaoning Province, PR China. tangchao314159@yahoo.com.cn
Xue
Hong-Li
HL
Bai
Chang-Lin
CL
Fu
Rong
R
D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000098:blood supply; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008315:Malondialdehyde / Q000032:analysis; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D027561:Salvia miltiorrhiza / Q000737:chemistry; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D045784:Abietanes; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C021751:tanshinone; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde