Protocatechuic aldehyde suppresses TNF-alpha-induced ICAM-1 and VCAM-1 expression in human umbilical vein endothelial cells.
Adhesion molecules, which play a crucial role in the development of atherogenesis, are produced by endothelial cells following stimulation with various inflammatory cytokines. The current studies examined the effect of a potent water-soluble antioxidant, protocatechuic aldehyde (derived from the Chinese herb, Salvia miltiorrhiza), on the expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor-alpha (TNF-alpha). Protocatechuic aldehyde appeared to specifically downregulate the TNF-alpha-induced cell surface expression of vascular adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) on HUVECs as well as the release of soluble VCAM-1and ICAM-1 from HUVECs in a dose-response manner at pharmacologically relevant concentrations (0.15-1.35 mM). We also observed a dose-dependent lowering of mRNA expression of VCAM-1 and ICAM-1 in the presence of protocatechuic aldehyde. Furthermore, protocatechuic aldehyde (0.15, 0.45, and 1.35 mM) notably inhibited TNF-alpha-induced upregulation of U937 cell adhesion to HUVECs to 83.7%, 60.9%, and 40.8%, respectively. A gel shift assay further showed that protocatechuic aldehyde inhibited the TNF-alpha-activated NF-kappaB and AP-1 DNA binding activities in a dose-dependent manner. Collectively, these results indicate that protocatechuic aldehyde inhibits TNF-alpha-stimulated VCAM-1 and ICAM-1expression in HUVECs through a mechanism that involves NF-kappaB and AP-1.
Zhou
Zhe
Z
Beijing Institute of Radiation Medicine, Haidian District, Beijing, PR China.
Liu
Yong
Y
Miao
Ai-Dong
AD
Wang
Sheng-Qi
SQ
D001547:Benzaldehydes / Q000494:pharmacology*; D015153:Blotting, Western; D002396:Catechols / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D020298:U937 Cells; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism
D001547:Benzaldehydes; D002396:Catechols; D019040:E-Selectin; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C005581:protocatechualdehyde