INDUCTION OF THE TRANSCRIPTION FACTOR IRF-1 AND INTERFERON-BETA MESSENGER-RNAS BY CYTOKINES AND ACTIVATORS OF 2ND-MESSENGER PATHWAYS
INDUCTION OF THE TRANSCRIPTION FACTOR IRF-1 AND INTERFERON-BETA MESSENGER-RNAS BY CYTOKINES AND ACTIVATORS OF 2ND-MESSENGER PATHWAYS
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DOI：
10.1073/pnas.86.24.9936
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发表时间：
1989-12-01
影响因子：
11.1
通讯作者：
VILCEK, J
中科院分区：
文献类型：
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作者：
FUJITA, T;REIS, LFL;VILCEK, J
核蛋白IRF-1（干扰素调节因子1）较早显示与干扰素（IFN）-α上存在的顺式作用调节元件结合。β的基因和基因IFN-诱导基因。在此，我们表明，在人FS-4和鼠L929细胞中，用肿瘤坏死因子（TNF）、白细胞介素1（IL-1）、聚（I）·聚（C）或IFN-β处理可增加IRF-1 mRNA的稳态水平。IRF-1 mRNA的诱导也表现在细胞与钙离子载体A23187或佛波醇12-肉豆蔻酸酯13-乙酸酯，但不与表皮生长因子，二丁酰-cAMP，或腺苷酸环化酶激活剂毛喉素处理。为了确定IRF-1 mRNA水平的刺激是否与IFN-β相关，诱导时，我们比较了IRF-1和IFN-β。暴露于各种刺激的细胞中的mRNA水平。在L929细胞中，在不能诱导显著水平的IFN-β的条件下用poly（I）·poly（C）处理。mRNA导致非常低的IRF-1 mRNA诱导，但是在加入poly（I）·poly（C）之前用IFN“引发”细胞大大增加了IRF-1和IFN-β。mRNA。在FS-4细胞中，IFN-β增加。在用TNF、IL-1、A23187或poly（I）·poly（C）处理后观察到mRNA（通过聚合酶链反应检测），但用IFN-β处理后未观察到，表皮生长因子、二丁酰-cAMP或毛喉素。因此，增加IFN-β稳态水平的所有治疗都是有效的。mRNA也能提高IRF-1 mRNA水平。然而，用IFN-β治疗，其引起IRF-1 mRNA的显著刺激，但不能产生可检测的IFN-β增加。mRNA。似乎IRF-1对于IFN-β可能是必需的，但不是充分的。诱导TNF和IL-1增加IRF-1和IFN-β的能力。mRNA可能是造成TNF、IL-1和IFN作用的某些相似性的原因。
Nuclear protein IRF-1 (interferon regulatory factor 1) was earlier shown to bind to cis-acting regulatory elements present on interferon (IFN)-.alpha./.beta. genes and genes IFN-inducible genes. Here we show that in both human FS-4 and murine L929 cells, steady-state levels of IRF-1 mRNA were increased by treatment with tumor necrosis factor (TNF), interleukin 1 (IL-1), poly(I).cntdot.poly(C), or IFN-.beta.. IRF-1 mRNA induction was also demonstrated in cells treated with calcium ionophore A23187 or with phorbol 12-myristate 13-acetate, but not with epidermal growth factor, dibutyryl-cAMP, or the adenylate cyclase activator forskolin. To determine whether stimulation of IRF-1 mRNA levels correlates with IFN-.beta. induction, we compared IRF-1 and IFN-.beta. mRNA levels in cells exposed to various stimuli. In L929 cells, treatment with poly(I).cntdot.poly(C) under conditions that failed to induce significant levels of IFN-.beta. mRNA led to a very low induction of IRF-1 mRNA, but "priming" cells with IFN prior to the addition of poly(I).cntdot.poly(C) greatly increased both IRF-1 and IFN-.beta. mRNAs. In FS-4 cells an increase in IFN-.beta. mRNA (examined by the polymerase chain reaction) was seen after treatment with TNF, IL-1, A23187, or poly(I).cntdot.poly(C), but not with IFN-.beta., epidermal growth factor, dibutyryl-cAMP, or forskolin. Thus, all treatments that increased steady-state levels of IFN-.beta. mRNA also enhanced IRF-1 mRNA levels. However, treatment with IFN-.beta., which caused a marked stimulation in IRF-1 mRNA, failed to produce a detectable increase IFN-.beta. mRNA. It appears that IRF-1 may be necessary but not sufficient for IFN-.beta. induction. The ability of TNF and IL-1 to increase both IRF-1 and IFN-.beta. mRNAs may be responsible for some similarities in the actions of TNF, IL-1, and the IFNs.