Salvianolic acid B attenuates plasminogen activator inhibitor type 1 production in TNF-alpha treated human umbilical vein endothelial cells.
Plasminogen activator inhibitor type 1 (PAI-1), which plays a role in the development of atherosclerosis, is produced by endothelial cells following stimulation with various inflammatory cytokines such as tumor necrosis factor (TNF-alpha). In the present study, we investigated the effects of a potent water-soluble antioxidant, salvianolic acid B (SalB; derived from the Chinese herb, Salvia miltiorrhiza), on the expression of PAI-1 in TNF-alpha-treated human umbilical vein endothelial cells (HUVECs). We found that SalB inhibited TNF-alpha-induced PAI-1 mRNA production and protein secretion in HUVECs. Treatment with SalB (0.05 and 0.15 microM) notably attenuated TNF-alpha induced expression of PAI-1 to 90.5% and 74.6%, respectively, after 12 h, and to 75.1% and 64.2%, respectively, after 18 h. We also observed a dose-dependent decrease in PAI-1 protein production in the presence of SalB. We then used pathway inhibitors to investigate which step of the TNF-alpha induced signaling pathway was targeted by SalB. We found that the c-Jun N-terminal kinase (JNK) inhibitor, SP600125, increased the inhibitory effects of SalB on TNF-alpha-induced PAI-1 secretion, whereas the nuclear factor-kappaB (NF-kappaB) inhibitor, emodin, and the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, did not. A gel shift assay further showed that SalB inhibited the TNF-alpha-activated NF-kappaB and AP-1 DNA binding activities in a dose-dependent manner. Collectively, these results indicate that the NF-kappaB and ERK-AP-1 pathways are possible targets of SalB in the regulation of TNF-alpha-stimulated PAI-1 production in HUVECs.
Zhou
Zhe
Z
Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China.
Liu
Yong
Y
Miao
Ai-Dong
AD
Wang
Sheng-Qi
SQ
D001572:Benzofurans / Q000494:pharmacology*; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism; D053630:Depsides
D001572:Benzofurans; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D010959:Tissue Plasminogen Activator; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C076944:salvianolic acid B; D053630:Depsides