Expression and regulation of intercellular adhesion molecule-1 (ICAM-1) in organotypic cultures of rat liver tissue

Abstract

Background/Aims: The objective of the present study was to analyze the expression and regulation of intercellular adhesion molecule-1 (ICAM-1) in organotypic cultures of rat liver slices, which preserve the normal microenvironment of liver cells. Methods: Rat liver slices were maintained in culture for 15 min to 24 h and examnied for ICAM-1 expression by immunohistochemistry and Western blotting in basal conditions and after stimulation with 1000 IU/ml interferon-γ (IFNγ), 1000 IU/ml tumor necrosis factor-α (TNFα) and 50 μg/ml endotoxin. Immunohistochemical results were evaluated using a semiquantitative scoring system. Results: In uncultured slices, ICAM-1 was not detected on hepatocytes. In unstimulated liver slices maintained in organotypic culture, ICAM-1 was induced at the surface of scattered hepatocytes (score at 15 min, 0.33±0.47 and at 24 h, 1.17±0.69). After 4 h of stimulation, a significant increase in ICAM-1 expression by hepatocytes and adjacent sinusoidal cells, but not by intra-hepatic biliary epithelial cells, was observed for IFNγ (score: 2.35±0.47) and endotoxin (score: 2.67±0.47), but not with TNFα (score: 0.66±0.47). After 24 h of stimulation, a further increase in the extent of ICAM-1 expression by hepatocytes was observed for IFNγ (score: 3.67±0.47) and endotoxin (score: 4.0±0.0), and a significant overexpression of ICAM-1 by hepatocytes was detectable after treatement with TNFα (score: 3.67±0.47). Conclusions: In rat liver organotypic cultures, TNFα, IFNγ and endotoxin induce the expression of ICAM-1 in hepatocytes and adjacent sinusoidal endothelial cells, but not in portal tracts.