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α‐Lipoic acid inhibits TNF‐a‐induced NF‐κB activation and adhesion molecule expression in human aortic endothelial cells
Author(s) -
ZHANG WEI-JIAN,
FREI BALZ
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0260com
Subject(s) - cell adhesion molecule , ascorbic acid , alpha lipoic acid , tumor necrosis factor alpha , glutathione , cell adhesion , intercellular adhesion molecule 1 , monocyte , chemistry , oxidative stress , microbiology and biotechnology , biochemistry , biology , immunology , cell , enzyme , food science
Endothelial activation and monocyte adhesion are initiating steps in atherogenesis thought to be caused in part by oxidative stress. The metabolic thiol antioxidant a‐lipoic acid has been suggested to be of therapeutic value in pathologies associated with redox imbalances. We investigated the role of (R)‐a‐lipoic acid (LA) vs. glutathione and ascorbic acid in tumor necrosis factor a (TNF‐a) ‐induced adhesion molecule expression and nuclear factor KB (NF‐κB) signaling in human aortic endothelial cells (HAEC). Preincubation of HAEC for 48 h with LA (0.05–1 mmol/l) dose‐dependently inhibited TNF‐a (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‐a‐induced mRNA expression of monocyte chemoat‐tractant protein‐1 but did not affect expression of TNF‐a receptor 1. Furthermore, LA dose‐dependently inhibited TNF‐a‐induced IκB kinase activation, subsequent degradation of IκB, the cytoplasmic NF‐κB inhibitor, and nuclear translocation of NF‐κB. In contrast, TNF‐a‐induced NF‐κB 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 ‐cys‐teine, 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 IκB/NF‐κB signaling pathway at the level, or upstream, of IκB kinase.—Zhang, W.‐J., Frei, B. α‐Lipoic acid inhibits TNF‐α‐induced NF‐κB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J . 15, 2423–2432 (2001)