INTERFERON-GAMMA INHIBITS MACROPHAGE APOLIPOPROTEIN-E PRODUCTION BY POSTTRANSLATIONAL MECHANISMS

被引:77
作者
BRAND, K [1 ]
MACKMAN, N [1 ]
CURTISS, LK [1 ]
机构
[1] Scripps Res Inst, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA
关键词
DIFFERENTIATION; INTRACELLULAR DEGRADATION; LYMPHOKINES; PHORBOL ESTER; THP-1; CELLS;
D O I
10.1172/JCI116425
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:2031 / 2039
页数:9
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