Ernst T J, Ritchie A R, Demetri G D, Griffin J D
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts.
J Biol Chem. 1989 Apr 5;264(10):5700-3.
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.
人类血液单核细胞在激活后会分泌多种细胞因子，包括两种造血生长因子，即粒细胞集落刺激因子（G-CSF）和单核细胞/巨噬细胞集落刺激因子（M-CSF）。这两种因子的基因可以协同表达，也可以独立表达。用佛波醇肉豆蔻酸酯或放线菌酮处理单核细胞会诱导这两种基因的表达，而脂多糖则选择性地、短暂地诱导G-CSF转录本。白细胞介素-3或粒细胞/单核细胞集落刺激因子选择性地诱导M-CSF转录本。通过细胞核连续转录分析以及对放线菌酮处理细胞的Northern印迹分析来估计mRNA半衰期，我们发现这两种基因的诱导是由于mRNA的稳定化。在静息单核细胞中，G-CSF和M-CSF的转录本水平都非常低。在用佛波醇肉豆蔻酸酯、放线菌酮、脂多糖或白细胞介素-3刺激后，这两种基因的估计转录速率并未增加。然而，M-CSF mRNA的半衰期增加到约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基因表达的调控可能涉及多种转录后机制。
