Albumin selectively inhibits TNF alpha-induced expression of vascular cell adhesion molecule-1 in human aortic endothelial cells.

OBJECTIVE: Leukocyte adhesion to, and transmigration across, the vascular endothelium are critical initiating steps in inflammation and atherosclerosis. We hypothesized that albumin, the major plasma protein, acts as an anti-inflammatory agent towards endothelial cells. METHODS AND
RESULTS: To test the hypothesis, we studied the effects of bovine serum albumin (BSA) on TNF alpha-induced expression of adhesion molecules in cultured human aortic endothelial cells (HAEC). We found that incubation of HAEC for 16 h with BSA (0.5-5%, w/v) dose-dependently inhibited TNF alpha-induced mRNA and protein expression of vascular cell adhesion molecule-1 (VCAM-1), but not intercellular adhesion molecule-1 nor E-selectin. Yeast recombinant human serum albumin exerted similar inhibitory effects on VCAM-1 expression, whereas gamma-globulin was ineffective. BSA also significantly inhibited TNF alpha-induced adhesion of monocytic THP-1 cells to HAEC in a dose-dependent manner. Furthermore, BSA strongly inhibited activation and nuclear translocation of the transcription factor, nuclear factor-kappa B (NF-kappa B). For example, the physiologically relevant concentration of 5% BSA inhibited NF-kappa B activation by 90+/-7%, VCAM-1 mRNA and protein expression by 81+/-4 and 80+/-13%, respectively, and THP-1 adhesion by 73+/-9% (n=3). The inhibitory effect of BSA on TNF alpha-induced VCAM-1 expression was not attenuated by inhibition of intracellular GSH synthesis.
CONCLUSIONS: Our data show that physiological concentrations of albumin selectively inhibit TNF alpha-induced upregulation of VCAM-1 expression and monocyte adhesion, most likely by inhibiting NF-kappa B activation in a GSH-independent manner.