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Title 

Glabridin suppresses intercellular adhesion molecule-1 expression in tumor necrosis factor-α-stimulated human umbilical vein endothelial cells by blocking sphingosine kinase pathway: implications of Akt, extracellular signal-regulated kinase, and nuclear

Authors 

Jong Soon KangYeo Dae YoonMi Hwa HanSang Bae HanKiho LeeKi Hoon LeeSong Kyu ParkHwan Mook Kim

Publisher 

American Society for Pharmacology and Experimental Therapeutics (ASPET)

Issue Date 

2006

Citation 

Molecular Pharmacology, vol. 69, no. 3, pp. 941-949

Keywords 

endothelial leukocyte adhesion molecule 1glabridinintercellular adhesion molecule 1mitogen activated protein kinaseprotein kinase Bsphingosine kinasetumor necrosis factor alphacell adhesionendothelium cellmolecule

Abstract 

(R)-4-(3,4-Dihydro-8,8-dimethyl)-2H,8H-benzo[1,2-b:3,4-b′] dipyran-3yl)-1,3-benzenediol (glabridin) is known to have antiinflammatory, antimicrobial, and cardiovascular protective activities. In the present study, we report the inhibitory effect of glabridin on intercellular adhesion molecule-1 (ICAM-1) expression in tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs). Glabridin inhibited THP-1 cell adhesion to HUVECs stimulated by TNF-α and cell surface expression of ICAM-1 in TNF-α-stimulated HUVECs. The mRNA expression of adhesion molecules, including ICAM-1, vascular cell adhesion molecule-1, and E-selectin, was also suppressed by glabridin. Further study demonstrated the inhibitory effect of glabridin on nuclear factor (NF)-κB/Rel DNA binding, inhibitory factor-κBα (IκBα), and IκBβ degradation, IκB kinase activation, and p65 nuclear translocation in TNF-α-stimulated HUVECs. Treatment of a variety of cell lines with glabridin revealed that inhibitory effect of glabridin on NF-κB/Rel activation is not cell type-specific, and both inducible and constitutive NF-κB/Rel activation was suppressed by glabridin treatment. Moreover, TNF-α-induced phosphorylation of Akt and extracellular signal-regulated kinase (ERK) was blocked by glabridin treatment in HUVECs. Glabridin also suppressed sphingosine-1-phosphate (S1P)-induced cell surface expression and mRNA expression of ICAM-1. Further study demonstrated that TNF-α-induced sphingosine kinase activity was inhibited by glabridin, and the inhibitory effect of glabridin on TNF-α-induced ICAM-1 expression was reversed by addition of exogenous S1P. Together, our results indicate that the inhibitory effect of glabridin on ICAM-1 expression might be mediated, at least in part, by inhibiting sphingosine kinase pathway and subsequent inhibition of signaling pathways, including Akt, ERK, and NF-κB/Rel signaling pathway.

ISSN 

0026-895X

Link 

http://dx.doi.org/10.1124/mol.105.017442

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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