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.[1]References
- Salvianolic acid B attenuates plasminogen activator inhibitor type 1 production in TNF-alpha treated human umbilical vein endothelial cells. Zhou, Z., Liu, Y., Miao, A.D., Wang, S.Q. J. Cell. Biochem. (2005) [Pubmed]
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