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
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- 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
- Jong Soon Kang; Yeo Dae Yoon; Mi Hwa Han; Sang Bae Han; Kiho Lee; Ki Hoon Lee; Song Kyu Park; Hwan Mook Kim
- Bibliographic Citation
- Molecular Pharmacology, vol. 69, no. 3, pp. 941-949
- Publication Year
- (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.
- Amer Soc Pharmacology Experimental Therapeutics
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- Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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