The effect of salvianolic acid B combined with laminar shear stress on TNF-alpha-stimulated adhesion molecule expression in human aortic endothelial cells.
The study was conducted to investigate the effect of Salvianolic acid B (Sal B) on TNF-alpha-stimulated adhesion molecule expression i.e. vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin in human aortic endothelial cells (HAECs) under laminar shear stress (LSS) condition. Exposure of HAECs to LSS (12 dynes/cm(2) for 6 h decreased the TNF-alpha-induced protein expression of adhesion molecules i.e. VCAM-1, ICAM-1 and E-selectin. Pre-treatment of HAECs with Sal B (10 microg/ml) then exposed to LSS (12 dynes/cm(2)) for 6 h significantly inhibited VCAM-1, ICAM-1 and E-selectin expression stimulated by TNF-alpha. Moreover, combined Sal B and LSS treatment inhibited the adhesiveness of monocytic U937 cells to TNF-alpha-stimulated HAECs. We further examined the molecular mechanisms and found that the combination of Sal B and LSS treatment dramatically inhibited TNF-alpha-induced NF-kappaB activation evidenced by IkappaBalpha degradation and p65 nuclear translocation in HAECs. This study provides the first biomechanopharmacological evidence that Sal B has a combination effect with LSS to reduce the expression of three adhesion molecules, leading to reduced monocyte adhesion to HAECs, at least in part, by inhibiting the NF-kappaB signaling pathway. Data from this study thus support the potential clinical application of Sal B in vascular inflammatory diseases.
Xie
Li Xia
LX
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
Durairajan
Siva Sundara Kumar
SS
Lu
Jia Hong
JH
Liu
Chen Li
CL
Kum
Wan Fung
WF
Wang
Yan
Y
Koo
Irene
I
Wu
Wei Kang
WK
Han
Dong
D
Lao
Fulong
F
Huang
Jian-Dong
JD
Li
Min
M
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001572:Benzofurans; D002448:Cell Adhesion / Q000187:drug effects; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D020298:U937 Cells / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D053630:Depsides
D000893:Anti-Inflammatory Agents; D001572:Benzofurans; D019040:E-Selectin; D018799:Intercellular Adhesion Molecule-1; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C076944:salvianolic acid B; D053630:Depsides