期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 194, 期 1, 页码 13-22出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2011.08.008
关键词
Adhesion molecules; Compound K; Ginsenoside; Integrin; Transendothelial migration
资金
- Ministry of Knowledge Economy
- Korea Research Foundation
- Korean Government (MEST)
- Medical & Bio-Materials Research Center
- Small and Medium Business Administration, Korea [S1072365]
- National Research Foundation of Korea
- Ministry of Education, Science and Technology [2009-0072534/2010-0016150]
- Korea Evaluation Institute of Industrial Technology (KEIT) [S1072365] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Human leukocyte endothelial adhesion and transmigration occur in the early stage of the pathogenesis of atherosclerosis. Vascular endothelial cells are targeted by pro-inflammatory cytokines modulating many gene proteins responsible for cell adhesion, thrombosis and inflammatory responses. This study examined the potential of compound K to inhibit the pro-inflammatory cytokine TNF-alpha, induction of monocyte adhesion onto TNF-alpha-activated human umbilical vein endothelial cells (HUVEC). HUVEC were cultured with 10 ng/ml TNF-alpha with individual ginsenosides of Rb1, Rc, Re, Rhl and compound K (CK). Ginsenosides at doses of <= 50 mu M did not show any cytotoxicity. TNF-alpha induced THP-1 monocyte adhesion to HUVEC, and such induction was attenuated by Rh1 and CK. Consistently, CK suppressed TNF-alpha-induced expression of HUVEC adhesion molecules of VCAM-1, ICAM-1 and E-selectin, and also Rhl showed a substantial inhibition. Rh1 and CK dampened induction of counter-receptors, alpha 4/beta 1 integrin VLA-4 and alpha L/beta 2 integrin LFA-1 in TNF-alpha-treated THP-1 cells. Additionally, CK diminished THP-1 secretion of MMP-9 required during transmigration, inhibiting transendothelial migration of THP-1 cells. CK blunted TNF-alpha-promoted IL-8 secretion of HUVEC and CXCR1 expression of THP-1 monocytes. Furthermore, INF-alpha-activated endothelial I kappa B phosphorylation and NF-kappa B nuclear translocation were disturbed by CK, and TNF-alpha induction of alpha 4/beta 1 integrin was abrogated by the NF-kappa B inhibitor SN50. These results demonstrate that CK exerts anti-atherogenic activity with blocking leukocyte endothelial interaction and transmigration through negatively mediating NF-kappa B signaling. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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