title: Albumin selectively inhibits TNF alpha-induced expression of vascular cell adhesion molecule-1 in human aortic endothelial cells.
abstract: 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.
  
  
  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.
authors.affiliation: Linus Pauling Institute, Oregon State University, 571 Weniger Hall, Corvallis, OR 97331, USA.
authors.forename: Wei-Jian
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Balz
authors.initials: B
authors.lastname: Frei
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001011:Aorta; D001161:Arteriosclerosis / Q000276:immunology* / Q000473:pathology; D015152:Blotting, Northern / Q000379:methods; D002448:Cell Adhesion; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D012710:Serum Albumin, Bovine