Induction of interleukin-12 (IL-12) by recombinant glycoprotein gp120 of human immunodeficiency virus type 1 in human monocytes/macrophages: Requirement of gamma interferon for IL-12 secretion

Induction of interleukin-12 (IL-12) by recombinant glycoprotein gp120 of human immunodeficiency virus type 1 in human monocytes/macrophages: Requirement of gamma interferon for IL-12 secretion
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DOI:
10.1128/jvi.70.6.4121-4124.1996
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发表时间:
1996-06-01
影响因子:
5.4
通讯作者:
Belardelli, F
Belardelli, F
中科院分区:
医学2区
文献类型:
--
作者:
Fantuzzi, L;Gessani, S;Belardelli, F

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我们研究了 I 型人类免疫缺陷病毒的 gp120 糖蛋白对人单核细胞和单核细胞来源的巨噬细胞中白细胞介素 12 (IL-12) 表达的影响。 gp120 处理后,在两种细胞类型中均观察到 IL-12 p35 和 p40 亚基 mRNA 的诱导。然后,我们通过使用仅识别 IL-12 异二聚体的酶联免疫吸附测定来评估细胞因子的分泌。在单独用 gp120 处理的单核细胞/巨噬细胞中未检测到 IL-12。在用γ干扰素(IFN-γ)引发并随后用gp120处理的巨噬细胞中发现一致的IL-12分泌。在用 gp120 刺激的 IFN-γ 引发的单核细胞中偶尔观察到低水平的 IL-12。巨噬细胞对 IFN-γ 的启动效应的反应比单核细胞更强,这与 IFN-γ 在巨噬细胞中比在单核细胞中诱导更强的对水泡性口炎病毒的抗病毒状态的发现是一致的。这些数据表明gp120是单核细胞/巨噬细胞中IL-12表达的诱导剂,并且IFN-γ是IL-12分泌的重要辅助因子,尤其是在分化的巨噬细胞中。
We studied the effects of the gp120 glycoprotein of human immunodeficiency virus type I on the expression of interleukin-12 (IL-12) in human monocytes and in monocyte-derived macrophages. Induction of the mRNA for both the p35 and p40 subunits of IL-12 was observed in both cell types after gp120 treatment. We then evaluated cytokine secretion by using an enzyme-linked immunosorbent assay which recognizes only the IL-12 heterodimer. No IL-12 was detected in monocytes/macrophages treated with gp120 alone. A consistent IL-12 secretion was found in macrophages primed with gamma interferon (IFN-gamma) and subsequently treated with gp120. Low levels of IL-12 were occasionally observed in IFN-gamma-primed monocytes stimulated with gp120. The greater response of macrophages than of monocytes to the priming effect of IFN-gamma was consistent with the finding that IFN-gamma induced a much stronger antiviral state to vesicular stomatitis virus in macrophages than in monocytes. These data indicate that gp120 is an inducer of IL-12 expression in monocytes/macrophages and that IFN-gamma is an essential cofactor for IL-12 secretion, especially in differentiated macrophages.