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 ho w the target lymphocyte itself can modulate macrophage apo E productio n. The lymphokine interferon-gamma (IFN) dramatically inhibited the ac cumulation 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 TH P-1 cells. Treatment with IFN did not change the steady-state levels o f apo E mRNA. Furthermore, in the presence of IFN no increased degrada tion or increased uptake of extracellular apo E was detected. Pulse-ch ase experiments indicated that IFN reduced the accumulation of extrace llular apo E and increased the degradation of intracellular apo E. The inhibitory effect of IFN on apo E production also was observed in hum an monocyte-derived macrophages. Thus, our data demonstrated that IFN inhibited macrophage apo E production by posttranslational mechanisms. This represents a previously uncharacterized immunoregulatory interac tion and lends further support to a relationship between lipid metabol ism and the immune system.