Homocysteine inhibits TNF-alpha-induced endothelial adhesion molecule expression and monocyte adhesion via nuclear factor-kappaB dependent pathway.
Cellular adhesion molecules play a pivotal role in the pathogenesis of atherosclerosis by mediating the adherence of blood leukocytes. Since hyperhomocysteinemia appears to be an independent risk factor for the development of atherosclerosis, in this study we investigated the effect of homocysteine on basal and TNF-alpha-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell-adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin) on human umbilical-vein endothelial cells. Incubation of endothelial cells with homocysteine resulted in dose-dependent reduction in TNF-alpha-induced (5 ng/ml) expression of VCAM-1, E-selectin, and ICAM-1 (the latter less pronounced). This effect was found to be specific since other thiol compounds-cysteine and glutathione-did not mimic homocysteine activity. Homocysteine attenuated TNF-alpha-stimulated U-937 adhesion to the endothelial monolayer and reduced TNF-alpha-induced activation of the transcription factor NF-kappaB, indicating that NF-kappaB inhibition may play a role in inhibiting expression of adhesion molecules in endothelial cells.
Stangl
V
V
Medizinische Klinik und Poliklinik, Schwerpunkt Kardiologie, Angiologie and Pneumologie, Charité der Humboldt-Universität, Campus Mitte, Berlin, Germany. verena.stangl@charite.de
Günther
C
C
Jarrin
A
A
Bramlage
P
P
Moobed
M
M
Staudt
A
A
Baumann
G
G
Stangl
K
K
Felix
S B
SB
D002448:Cell Adhesion; D002478:Cells, Cultured; D003545:Cysteine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000096:biosynthesis; D004727:Endothelium / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006710:Homocysteine / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D016133:Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D020298:U937 Cells; D014470:Umbilical Cord / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D019040:E-Selectin; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D006710:Homocysteine; D018799:Intercellular Adhesion Molecule-1; D005978:Glutathione; D003545:Cysteine