Inflammatory cytokines up-regulate intercellular adhesion molecule-1 expression on primary cultured mouse hepatocytes and T-lymphocyte adhesion.
We investigated the effect of inflammatory cytokines on the intercellular adhesion molecule-1 expression on primary cultured murine hepatocytes. Tumor necrosis factor-alpha, interferon-gamma and interleukin-1 alpha up-regulated the intercellular adhesion molecule-1 expression on hepatocytes in a dose-dependent fashion; however, interleukin-6 did not. On the basis of kinetic analysis, the expression level reached a peak 24 hr after stimulation, and both cycloheximide and actinomycin D inhibited the expression. Furthermore, T lymphocytes bind more to interferon-gamma-stimulated hepatocytes than to unstimulated hepatocytes. The binding was dependent on the concentration of interferon-gamma. The binding was also up-regulated by stimulating T lymphocytes with phorbol myristate acetate. Tumor necrosis factor-alpha and interleukin-1 alpha demonstrated the same effect as interferon-gamma, whereas interleukin-6 did not increase T-lymphocyte adhesion to the hepatocytes. The adhesion induced by interferon-gamma or tumor necrosis factor-alpha was inhibited by antibody against either intercellular adhesion molecule-1 or lymphocyte function-associated antigen-1, a ligand for intercellular adhesion molecule-1, but was not inhibited by CD44 antibodies. These results demonstrate that inflammatory lymphokines enhance the T-lymphocyte adhesion to primary cultured hepatocytes by up-regulating the intercellular adhesion molecule-1 expression on the stimulated hepatocytes by activating the de novo pathway. This mechanism may play an important role in the pathogenesis of hepatitis.
Morita
M
M
Department of Biomolecular Engineering, Tokyo Institute of Technology, Yokohama, Japan.
Watanabe
Y
Y
Akaike
T
T
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D003609:Dactinomycin / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology; D015854:Up-Regulation
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D003609:Dactinomycin; D007371:Interferon-gamma; D003513:Cycloheximide