Albumin selectively inhibits TNFα-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 TNFalpha-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 TNFalpha-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 TNFa-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, unclear factor-kappaB (NF-kappaB). For example, the physiologically relevant concentration of 5% BSA inhibited NF-kappaB activation by 90 +/- 7% VCAM-1 mRNA and protein expression by 81 +/- 4 and 80 +/- 13%, respective, and THP-1 adhesion by 73 +/- 9% (n = 3). The inhibitory effect of BSA on TNFalpha-induced VCAM-1 expression was not attenuated by inhibition of intracellular GSH synthesis. Conclusions: Our data show that physiological concentrations of albumin selectively inhibit TNFalpha-induced upregulation of VCAM-1 expression and monocyte adhesion, most likely by inhibiting NF-kappaB activation in a GSH-independent manner. (C) 2002 Elsevier Science B.V. All rights reserved.