Immune modulation of adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58) in human hepatocytic cell lines.
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.
Kvale
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D
Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), National Hospital, Rikshospitalet, University of Oslo, Norway.
Brandtzaeg
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P
D015703:Antigens, CD / Q000032:analysis*; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis*
D015703:Antigens, CD; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1