Interferon-gamma inhibits macrophage apolipoprotein E production by posttranslational mechanisms.
Macrophage-derived apolipoprotein (apo) E and multimers of a synthetic apo E-peptide display monokine-like functions by inhibiting mitogen- or antigen-driven lymphocyte proliferation. This study demonstrated how the target lymphocyte itself can modulate macrophage apo E production. The lymphokine interferon-gamma (IFN) dramatically inhibited the accumulation of apo E in the supernatant of human monocytic THP-1 cells when present during phorbol myristate acetate-induced differentiation. A similar effect was observed when IFN was added to differentiated THP-1 cells. Treatment with IFN did not change the steady-state levels of apo E mRNA. Furthermore, in the presence of IFN no increased degradation or increased uptake of extracellular apo E was detected. Pulse-chase experiments indicated that IFN reduced the accumulation of extracellular apo E and increased the degradation of intracellular apo E. The inhibitory effect of IFN on apo E production also was observed in human monocyte-derived macrophages. Thus, our data demonstrated that IFN inhibited macrophage apo E production by posttranslational mechanisms. This represents a previously uncharacterized immunoregulatory interaction and lends further support to a relationship between lipid metabolism and the immune system.
Brand
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Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Mackman
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N
Curtiss
L K
LK
D001057:Apolipoproteins E / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D015342:DNA Probes; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001057:Apolipoproteins E; D015342:DNA Probes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate