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Glabridin suppresses intercellular adhesion molecule-1 expression in tumor necrosis factor-alpha-stimulated human umbilical vein endothelial cells by blocking sphingosine kinase pathway: implications of Akt, extracellular signal-regulated kinase, and nuclear factor-kappaB/Rel signaling pathways.
Mol Pharmacol. 2006 Mar; 69(3):941-9.MP

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 anti-inflammatory, 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-alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells (HUVECs). Glabridin inhibited THP-1 cell adhesion to HUVECs stimulated by TNF-alpha and cell surface expression of ICAM-1 in TNF-alpha-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)-kappaB/Rel DNA binding, inhibitory factor-kappaB alpha (IkappaB alpha), and IkappaB beta degradation, IkappaB kinase activation, and p65 nuclear translocation in TNF-alpha-stimulated HUVECs. Treatment of a variety of cell lines with glabridin revealed that inhibitory effect of glabridin on NF-kappaB/Rel activation is not cell type-specific, and both inducible and constitutive NF-kappaB/Rel activation was suppressed by glabridin treatment. Moreover, TNF-alpha-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-alpha-induced sphingosine kinase activity was inhibited by glabridin, and the inhibitory effect of glabridin on TNF-alpha-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-kappaB/Rel signaling pathway.

Authors+Show Affiliations

Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Taejon, 305-333, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16354764

Citation

Kang, Jong Soon, et al. "Glabridin Suppresses Intercellular Adhesion Molecule-1 Expression in Tumor Necrosis Factor-alpha-stimulated Human Umbilical Vein Endothelial Cells By Blocking Sphingosine Kinase Pathway: Implications of Akt, Extracellular Signal-regulated Kinase, and Nuclear factor-kappaB/Rel Signaling Pathways." Molecular Pharmacology, vol. 69, no. 3, 2006, pp. 941-9.
Kang JS, Yoon YD, Han MH, et al. Glabridin suppresses intercellular adhesion molecule-1 expression in tumor necrosis factor-alpha-stimulated human umbilical vein endothelial cells by blocking sphingosine kinase pathway: implications of Akt, extracellular signal-regulated kinase, and nuclear factor-kappaB/Rel signaling pathways. Mol Pharmacol. 2006;69(3):941-9.
Kang, J. S., Yoon, Y. D., Han, M. H., Han, S. B., Lee, K., Lee, K. H., Park, S. K., & Kim, H. M. (2006). Glabridin suppresses intercellular adhesion molecule-1 expression in tumor necrosis factor-alpha-stimulated human umbilical vein endothelial cells by blocking sphingosine kinase pathway: implications of Akt, extracellular signal-regulated kinase, and nuclear factor-kappaB/Rel signaling pathways. Molecular Pharmacology, 69(3), 941-9.
Kang JS, et al. Glabridin Suppresses Intercellular Adhesion Molecule-1 Expression in Tumor Necrosis Factor-alpha-stimulated Human Umbilical Vein Endothelial Cells By Blocking Sphingosine Kinase Pathway: Implications of Akt, Extracellular Signal-regulated Kinase, and Nuclear factor-kappaB/Rel Signaling Pathways. Mol Pharmacol. 2006;69(3):941-9. PubMed PMID: 16354764.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glabridin suppresses intercellular adhesion molecule-1 expression in tumor necrosis factor-alpha-stimulated human umbilical vein endothelial cells by blocking sphingosine kinase pathway: implications of Akt, extracellular signal-regulated kinase, and nuclear factor-kappaB/Rel signaling pathways. AU - Kang,Jong Soon, AU - Yoon,Yeo Dae, AU - Han,Mi Hwa, AU - Han,Sang-Bae, AU - Lee,Kiho, AU - Lee,Ki Hoon, AU - Park,Song-Kyu, AU - Kim,Hwan Mook, Y1 - 2005/12/14/ PY - 2005/12/16/pubmed PY - 2006/4/20/medline PY - 2005/12/16/entrez SP - 941 EP - 9 JF - Molecular pharmacology JO - Mol Pharmacol VL - 69 IS - 3 N2 - (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 anti-inflammatory, 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-alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells (HUVECs). Glabridin inhibited THP-1 cell adhesion to HUVECs stimulated by TNF-alpha and cell surface expression of ICAM-1 in TNF-alpha-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)-kappaB/Rel DNA binding, inhibitory factor-kappaB alpha (IkappaB alpha), and IkappaB beta degradation, IkappaB kinase activation, and p65 nuclear translocation in TNF-alpha-stimulated HUVECs. Treatment of a variety of cell lines with glabridin revealed that inhibitory effect of glabridin on NF-kappaB/Rel activation is not cell type-specific, and both inducible and constitutive NF-kappaB/Rel activation was suppressed by glabridin treatment. Moreover, TNF-alpha-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-alpha-induced sphingosine kinase activity was inhibited by glabridin, and the inhibitory effect of glabridin on TNF-alpha-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-kappaB/Rel signaling pathway. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/16354764/Glabridin_suppresses_intercellular_adhesion_molecule_1_expression_in_tumor_necrosis_factor_alpha_stimulated_human_umbilical_vein_endothelial_cells_by_blocking_sphingosine_kinase_pathway:_implications_of_Akt_extracellular_signal_regulated_kinase_and_nuclear_factor_kappaB/Rel_signaling_pathways_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16354764 DB - PRIME DP - Unbound Medicine ER -