TitleAlpha-lipoic acid inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in human aortic endothelial cells.
Publication TypeJournal Article
Year of Publication2001
AuthorsZhang WJ, Frei B
JournalFASEB J
Date Published2001 Nov
KeywordsAorta, Ascorbic Acid, Cell Adhesion Molecules, Cell Line, Chemokine CCL2, Dose-Response Relationship, Drug, E-Selectin, Endothelium, Vascular, Gene Expression Regulation, Glutathione, Humans, I-kappa B Proteins, NF-kappa B, Phosphorylation, RNA, Messenger, Thioctic Acid, Time Factors, Vascular Cell Adhesion Molecule-1

Endothelial activation and monocyte adhesion are initiating steps in atherogenesis thought to be caused in part by oxidative stress. The metabolic thiol antioxidant alpha-lipoic acid has been suggested to be of therapeutic value in pathologies associated with redox imbalances. We investigated the role of (R)-alpha-lipoic acid (LA) vs. glutathione and ascorbic acid in tumor necrosis factor alpha (TNF-alpha) -induced adhesion molecule expression and nuclear factor kappaB (NF-kappaB) signaling in human aortic endothelial cells (HAEC). Preincubation of HAEC for 48 h with LA (0.05-1 mmol/l) dose-dependently inhibited TNF-alpha (10 U/ml) -induced adhesion of human monocytic THP-1 cells, as well as mRNA and protein expression of E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1. LA also strongly inhibited TNF-alpha-induced mRNA expression of monocyte chemoattractant protein-1 but did not affect expression of TNF-alpha receptor 1. Furthermore, LA dose-dependently inhibited TNF-alpha-induced IkappaB kinase activation, subsequent degradation of IkappaB, the cytoplasmic NF-kappaB inhibitor, and nuclear translocation of NF-kappaB. In contrast, TNF-alpha-induced NF-kappaB activation and adhesion molecule expression were not affected by ascorbic acid or by manipulating cellular glutathione status with l-2-oxo-4-thiazolidinecarboxylic acid, N-acetyl-l-cysteine, or d,l-buthionine-S,R-sulfoximine. Our data show that clinically relevant concentrations of LA, but neither vitamin C nor glutathione, inhibit adhesion molecule expression in HAEC and monocyte adhesion by inhibiting the IkappaB/NF-kappaB signaling pathway at the level, or upstream, of IkappaB kinase.

Alternate JournalFASEB J.
PubMed ID11689467
Grant ListHL-56170 / HL / NHLBI NIH HHS / United States
HL-60886 / HL / NHLBI NIH HHS / United States