Horiguchi J, Sariban E, Kufe D
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Mol Cell Biol. 1988 Sep;8(9):3951-4. doi: 10.1128/mcb.8.9.3951-3954.1988.
Regulation of CSF-1 gene expression was investigated in human monocytes. CSF-1 transcripts were at low or undetectable levels in resting monocytes. However, in monocytes treated with 12-O-tetradecanoylphorbol-13-acetate (TPA), CSF-1 mRNA was increased by 3 h and reached maximal levels by 12 h of drug exposure. When nuclear run-on assays were used, CSF-1 gene transcription was also at low or undetectable levels in resting monocytes but was activated after TPA exposure. TPA-treated monocytes exposed to actinomycin D further demonstrated that the half-life of the CSF-1 mRNA is 0.9 h. The results also demonstrated that the protein synthesis inhibitor, cycloheximide (CHX), increases CSF-1 mRNA levels in both resting and TPA-treated monocytes. These effects of CHX occurred in the absence of detectable increases in CSF-1 gene transcription. Moreover, treatment of monocytes with CHX and actinomycin D demonstrated that inhibition of protein synthesis is associated with stabilization of the CSF-1 transcript. Taken together, these findings indicated that CSF-1 gene expression is controlled at both transcriptional and posttranscriptional levels in human monocytes.
在人类单核细胞中研究了集落刺激因子-1（CSF-1）基因表达的调控。在静息单核细胞中，CSF-1转录本水平较低或无法检测到。然而，在用12-氧十四烷酰佛波醇-13-乙酸酯（TPA）处理的单核细胞中，CSF-1 mRNA在3小时时增加，并在药物暴露12小时时达到最高水平。当使用核转录分析时，CSF-1基因转录在静息单核细胞中也处于低水平或无法检测到，但在TPA暴露后被激活。用放线菌素D处理TPA刺激的单核细胞进一步表明，CSF-1 mRNA的半衰期为0.9小时。结果还表明，蛋白质合成抑制剂环己酰亚胺（CHX）可增加静息和TPA处理的单核细胞中CSF-1 mRNA的水平。CHX的这些作用在CSF-1基因转录未检测到增加的情况下发生。此外，用CHX和放线菌素D处理单核细胞表明，蛋白质合成的抑制与CSF-1转录本的稳定有关。综上所述，这些发现表明，CSF-1基因表达在人类单核细胞的转录和转录后水平均受到控制。
