Immune modulation of adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58) in human hepatocytic cell lines

Abstract

Interactions between leukocytes such as T cells and accessory or target cells are promoted by adhesion molecules, in particular intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-3 (LFA-3). Hepatocytes are usually negative for these surface membrane proteins which, however, may be up-regulated in inflammatory processes within the liver. Because the regulatory signals for, and tissue distribution of, these adhesion molecules vary among different tissues, expression of ICAM-1 and LFA-3 was studied in the Hep-G2 and SK-Hep-1 human hepatocytic cell lines in vitro. Low, constitutive membrane expression of the two molecules was detected in both cell lines. ICAM-1, but not LFA-3, was rapidly up-regulated by interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF), and to some extent by interferon-gamma (IFN) and IL-6, whereas IL-4 had variable low effects, if any. Considerable synergism on ICAM-1 protein levels was observed after stimulation with TNF, IL-1, and IFN, whereas co-incubation with actinomycin D abolished these effects. ICAM-1 mRNA levels increased 16-20 times after cytokine incubation. Our data indicated that hepatocytes share the regulatory pathways for ICAM-1 described for several other cell types. Absence of these molecules in vivo may reflect a dominance of negative modulation signals in the normal liver, which might also explain the low levels of HLA class I molecules.