Antioxidants inhibit monocyte adhesion by suppressing nuclear factor-kappa B mobilization and induction of vascular cell adhesion molecule-1 in endothelial cells stimulated to generate radicals.
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Discussion
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Implication
In vitro study demonstrates that antioxidants reduce monocyte adhesion in TNF-stimulated endothelial cells, indicating radical-mediated regulation of VCAM-1 via NF-kappa B.
Key Points
- To examine how antioxidants and reactive oxygen species regulate TNF-induced VCAM-1 and ICAM-1 expression and subsequent monocyte adhesion in human endothelial cells.
- Treated human umbilical vein endothelial cells (HUVECs) and human umbilical arterial endothelial cells with TNF in the presence or absence of antioxidants (PDTC, N-acetylcysteine) or radical-generating enzyme inhibitors (apocynin, SKF525a).
- Quantified VCAM-1 and ICAM-1 surface protein and mRNA expression using flow cytometry and PCR, and evaluated NF-kappa B activation via gel-shift analysis.
- Assessed monocytic U937 cell adhesion to TNF-activated HUVECs and verified VCAM-1 dependence using anti-VCAM-1 monoclonal antibody 1G11.
- PDTC dose-dependently reduced TNF-induced VCAM-1 surface protein and mRNA expression by 70% at 100 mumol/L and blocked NF-kappa B mobilization without affecting ICAM-1 induction.
- Inhibition of radical-generating systems via apocynin (NADPH oxidase inhibitor) and SKF525a (cytochrome P-450 inhibitor) selectively suppressed TNF-induced VCAM-1 expression.
- PDTC (100 mumol/L) reduced U937 monocyte adhesion to TNF-treated HUVECs by 75%, an effect replicated by apocynin, SKF525a, and anti-VCAM-1 antibody blockade.
Cite This Study
Weber et al. (1994) studied this question.