Regulation of granulocyte- and monocyte-colony stimulating factor mRNA levels in human blood monocytes is mediated primarily at a post-transcriptional level.
Regulation of granulocyte- and monocyte-colony stimulating factor mRNA levels in human blood monocytes is mediated primarily at a post-transcriptional level.
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DOI：
10.1016/s0021-9258(18)83605-5
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发表时间：
1989-04
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影响因子：
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通讯作者：
T. J. Ernst;Ann R. Ritchie;G. Demetri;James D. Griffins
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作者：
T. J. Ernst;Ann R. Ritchie;G. Demetri;James D. Griffins
人血液单核细胞在激活后分泌多种细胞因子，包括两种造血生长因子，粒细胞集落刺激因子（G-CSF）和单核/巨噬细胞集落刺激因子（M-CSF）。这两个因子的基因既可以协调表达，也可以独立表达。单核细胞用佛波肉豆蔻酸或环己亚胺处理可诱导这两个基因，而脂多糖可选择性和短暂地诱导G-CSF转录物。白细胞介素-3或粒细胞/单核细胞集落刺激因子选择性诱导M-CSF转录物。利用放线菌素d处理细胞的核运行转录分析和Northern blot分析来估计mRNA的半衰期，我们发现这两个基因的诱导都是由于mRNA的稳定。在静止的单核细胞中，G-CSF和M-CSF的转录本水平都很低。在用佛波肉豆蔻酸、环己亚胺、脂多糖或白介素-3刺激后，两种基因的转录率都没有增加。然而，M-CSF mRNA的半衰期增加到大约2小时，而G-CSF mRNA的半衰期增加到长达4小时。因此，单核细胞中CSF基因表达的控制可能涉及不止一种转录后机制。
Human blood monocytes secrete a number of cytokines following activation including two hematopoietic growth factors, granulocyte-colony stimulating factor (G-CSF) and monocyte/macrophage-colony stimulating factor (M-CSF). The genes for these two factors can be both coordinately and independently expressed. Treatment of monocytes with phorbol myristic acid or cycloheximide induces both genes, while lipopolysaccharide selectively and transiently induces G-CSF transcripts. Interleukin-3 or granulocyte/monocyte-colony stimulating factor selectively induce M-CSF transcripts. Using nuclear run-on transcription assays and Northern blot analysis of actinomycin D-treated cells to estimate mRNA half-life, we show that the induction of both genes is due to mRNA stabilization. In resting monocytes, the levels of transcripts for both G-CSF and M-CSF are very low. Following stimulation with phorbol myristic acid, cycloheximide, lipopolysaccharide, or interleukin-3 the estimated transcription rate of both genes does not increase. However, the half-life of M-CSF mRNA increases to approximately 2 h, whereas G-CSF mRNA half-life increases to as long as 4 h. Thus, the control of CSF gene expression in monocytes is likely to involve more than one post-transcriptional mechanism.