Cytokine regulation of TNF-alpha mRNA and protein production by unprimed macrophages from C57Bl/6 and NZW mice.
Cytokine regulation of TNF-alpha mRNA and protein production by unprimed macrophages from C57Bl/6 and NZW mice.
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C57Bl/6 和 NZW 小鼠未引发的巨噬细胞对 TNF-α mRNA 和蛋白质产生的细胞因子调节。
DOI：
10.1002/jlb.56.4.514
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发表时间：
1994
影响因子：
5.5
通讯作者：
Jongeneel,CV
中科院分区：
文献类型：
--
作者：
Schook,LB;Albrecht,H;Gallay,P;Jongeneel,CV
众所周知，细菌脂多糖（LPS）诱导原代单核细胞和巨噬细胞合成肿瘤坏死因子α（TNF-α）和其它炎性细胞因子，并且Thl淋巴因子、白细胞介素-2（IL-2）和干扰素-γ（IFN-γ）增强这种应答。我们研究了IL-2和IFN-γ独立于LPS诱导TNF-αmRNA和蛋白产生的能力，以及巨噬细胞集落刺激因子（M-CSF）和IL-10对这种反应的调节。我们发现IL-2和IFN-γ都能诱导TNF-αmRNA的积累，尽管动力学比LPS慢，但它们具有协同作用。然而，淋巴因子刺激的巨噬细胞分泌很少的TNF生物活性，除非还加入LPS。这一发现强调了翻译效应在控制TNF产生中的重要性。M-CSF和IL-10在mRNA和生物活性水平上强烈抑制TNF的产生，但对IL-6的产生没有影响。来自NZW小鼠品系的骨髓衍生的或硫代糖酸盐诱导的巨噬细胞（已报道其产生TNF的能力不足）至少与来自C57 B1/6品系的巨噬细胞一样对LPS或淋巴因子有反应，并且类似地受到M-CSF和IL-10的影响。因此，NZW小鼠的遗传缺陷不是TNF产生的主要缺陷。Leukoc 56：514-520; 1994.
It is well known that bacterial lipopolysaccharide (LPS) induces the synthesis of tumor necrosis factorα(TNF-α) and other inflammatory cytokines by primary monocytes and macrophages and that the Thl lymphokines, interleukin-2 (IL-2) and interferon-γ(IFN-γ), augment this response. We investigated the ability of IL-2 and IFN-γto induce the production of TNF-αmRNA and protein independently of LPS and the modulation of this response by macrophage colony-stimulating factor (M-CSF) and IL-10. We found that IL-2 and IFN-γwere both able to induce the accumulation of TNF-αmRNA, albeit with slower kinetics than LPS, and that they acted synergistically. However, very little TNF bioactivity was secreted by lymphokine-stimulated macrophages unless LPS was also added. This finding underscores the importance of translational effects in the control of TNF production. M-CSF and IL-10 strongly inhibited TNF production at the level of both mRNA and bioactivity but had no effect on the production of IL-6. Bone marrow-derived or thiogycollate-elicited macrophages from the NZW mouse strain, which have been reported to be deficient in their ability to produce TNF, were at least as responsive to LPS or lymphokines as those taken from the C57B1/6 strain and were similarly affected by M-CSF and IL-10. Therefore, the genetic defect of NZW mice is not a primary deficiency in TNF productionJ. Leukoc. Biol.56: 514–520; 1994.