Zubiaga A M, Muñoz E, Huber B T
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111.
J Immunol. 1991 Jun 1;146(11):3857-63.
Lymphokine production is regulated both at the transcriptional and the posttranscriptional level. To date, it has been shown that the protein synthesis inhibitor cycloheximide (CHX) up-regulates IL-2 expression in T cells by stabilizing its mRNA. In this report we have examined the effect of CHX on IL-2 at the transcriptional level. We have found that CHX has a positive regulatory function in IL-2 transcription, which is dependent on prior activation of this gene. This is not due to posttranslational conversion of inactive NFkB into its active form by CHX, because a clustered mutation in the kB-like sequence in the IL-2 enhancer that abrogates NFkB binding does not affect the up-regulation of IL-2 transcription. These results favor the hypothesis that, in addition to positive factors, negative elements regulate IL-2 transcription. Furthermore, we have tested the effect of CHX on IL-4 and granulocyte-macrophage-CSF transcription of both lymphokines. These results suggest that transcriptional up-regulation by CHX may be specific for IL-2 with respect to lymphokine expression.
淋巴细胞因子的产生在转录水平和转录后水平均受到调控。迄今为止，已有研究表明，蛋白质合成抑制剂环己酰亚胺（CHX）通过稳定其信使核糖核酸（mRNA）来上调T细胞中白细胞介素-2（IL-2）的表达。在本报告中，我们研究了CHX在转录水平对IL-2的影响。我们发现，CHX在IL-2转录中具有正调控功能，这依赖于该基因的预先激活。这并非是由于CHX将无活性的核因子κB（NFκB）翻译后转化为其活性形式，因为IL-2增强子中κB样序列的簇状突变消除了NFκB的结合，但并不影响IL-2转录的上调。这些结果支持了这样一种假说，即除了正性因子外，负性元件也调控IL-2转录。此外，我们还测试了CHX对这两种淋巴细胞因子的IL-4和粒细胞-巨噬细胞集落刺激因子（GM-CSF）转录的影响。这些结果表明，就淋巴细胞因子表达而言，CHX对IL-2转录的上调作用可能具有特异性。
