Journal
ATHEROSCLEROSIS
Volume 211, Issue 1, Pages 77-83Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2010.01.040
Keywords
5 '-NIO; Atherosclerosis; Inflammation; Human vascular endothelial cell; MCP-1; IL-8; ICAM-1; TNF-alpha
Funding
- MOST/KOSEF [R13-2005-013-01000-0]
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Inflammation plays a critical role in the development of atherosclerosis and TNF-alpha, a major inflammatory cytokine, induces inflammatory responses by enhancing the expression of adhesion molecules and the secretion of inflammatory mediators. Indirubin is an active compound of Polygonum tinctorium Lour (P. tinctorium) that has the ability to suppress inflammation. Previously, we described the novel indirubin derivative, 5'-nitro-indirubinoxime (5'-NIO), and demonstrated that it has potent anti-proliferative activity against various human cancer cells. In this study, we examined the effect of 5'-NIO on the TNF-alpha induced inflammatory conditions of human umbilical vein endothelial cells (HUVECs). We found that 5'-NIO inhibited TNF-alpha induced MCP-1 and IL-8 expression at the RNA and protein levels in HUVECs. Specifically, 5'-NIO significantly inhibited the TNF-alpha stimulated release of MCP-1 and IL-8, with levels that were only 19.8% and 30.9% of those of untreated control cells, respectively. Furthermore, 5'-NIO largely inhibited the adhesion of U937 cells to HUVECs by decreasing the expression level of ICAM-1 and VCAM-1. Overall, these observations suggest that 5'-NIO has the potential for use as an anti-atherosclerotic agent. (C ) 2010 Elsevier Ireland Ltd. All rights reserved.
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