Regulation of Granulocyte- and Monocyte-colony Stimulating Factor mRNA Levels in Human Blood Monocytes Is Mediated Primarily at a Post-transcriptional Level

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 exp...

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Bibliographic Details
Published in:The Journal of biological chemistry 1989-04, Vol.264 (10), p.5700-5703
Main Authors: Ernst, T J, Ritchie, A R, Demetri, G D, Griffin, J D
Format: Article
Language:English
Subjects:
Biological and medical sciences
Colony-Stimulating Factors - genetics
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Genes
Granulocyte-Macrophage Colony-Stimulating Factor
Granulocytes - physiology
Growth Substances - genetics
Humans
Kinetics
Macrophage Colony-Stimulating Factor
Molecular and cellular biology
Molecular genetics
Monocytes - metabolism
Plasmids
RNA, Messenger - biosynthesis
RNA, Messenger - blood
RNA, Messenger - genetics
Transcription, Genetic
Transcription. Transcription factor. Splicing. Rna processing
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(18)83605-5