Regulation of Interleukin-l 2 Expression in Human Monocytes : Selective Priming by Interferon-y of Lipopolysaccharide-Inducible p 35 and p 40 Genes

Regulation of Interleukin-l 2 Expression in Human Monocytes : Selective Priming by Interferon-y of Lipopolysaccharide-Inducible p 35 and p 40 Genes
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人单核细胞中白介素-1 2 表达的调节:脂多糖诱导性 p 35 和 p 40 基因的干扰素-y 选择性引发

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发表时间:
2000
期刊:
影响因子:
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通讯作者:
M. Norcross
M. Norcross
中科院分区:
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文献类型:
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作者:
Jinhai Wang;M. Norcross

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白细胞介素L2(IL-12)是一种非细胞巨噬细胞衍生的细胞因子,对T淋巴细胞和自然杀伤细胞的活动和功能至关重要。在这项研究中,我们检测了细菌脂多糖(LPS)对人单核细胞IL-12表达的调节。文中展示了从单核细胞诱导IL-12的几个新方面。IL-12rnRNA的最佳表达和生物活性需要在内毒素刺激前用干扰素-γ(IFN-y)特异性地激活单核细胞。粒细胞巨噬细胞集落刺激因子(GM-CSF)对内毒素诱导的肿瘤坏死因子(TNF)和IL-12p40 m RNA具有同等的启动刺激作用,但对内毒素诱导的p35信号和分泌IL-12活性较差。巨噬细胞集落刺激因子(M-CSF)虽然是单核细胞的有效生存因子,但对IL-12的产生没有启动活性。时程实验表明,干扰素-I和脂多糖对p40和p35有独立的调节作用。只需短暂接触干扰素-γ(2小时)即可诱导p40的表达,
Interleukin-l2 (IL-12) is a rnonocytelmacrophage-derived cytokine that is critical for T lymphocyte and natural killer cell activities and functions. In this tudy, we examined the regulation of IL-12 expression by human monocytes in response t o bacterial lipopolysaccharide (LPS). Several novel aspects of IL-12 induction from monocytes were shown. Optimal expression of IL-12 rnRNA and bioactivity required specific priming of monocytes by interferon-y (IFN-y) before LPS stimulation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) provided an equivalent priming stimulus for LPS-induced tumor necrosis factor (TNF) and IL-12 p40 mRNA, but primed poorly for LPS-inducible p35 message and secreted IL-12 activity. Macrophage colony-stimulating factor (M-CSF), although a potent survival factor for monocytes, showed no priming activity for IL-12 production. Time course experiments demonstrated independent regulation of p40 and p35 by IFN-)I and LPS. LPS inducibility of p40 expression required only a brief exposure to IFN-y (2 hours),
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