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Interferon-gamma destabilizes interleukin-1-induced granulocyte-macrophage colony-stimulating factor mRNA in murine
1Division of Cytokine Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892.
Vascular endothelial cells can affect hematopoiesis by releasing granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, we show that GM-CSF production in murine aorta-derived vascular endothelial cells is regulated by two cytokines:interleukin-1 (IL-1), which induces the production of GM-CSF, and interferon gamma (IFN-gamma), which downregulates this production. The GM-CSF gene is constitutively transcribed in these cells and the transcription rate of the GM-CSF gene does not change with either IL-1 alone or IL-1 plus IFN-gamma. Whereas IL-1 treatment increases the GM-CSF mRNA half-life, simultaneous treatment with IL-1 plus IFN-gamma results in a decrease in the mRNA half-life. IL-1 also enhances IL-6 mRNA accumulation in these cells, although by increasing its transcription rate. In this case, IFN-gamma does not affect IL-6 mRNA expression. These data suggest that IL-1-induced GM-CSF expression in endothelial cells is regulated at the posttranscriptional level and that IFN-gamma specifically inhibits GM-CSF expression via destabilization of the mRNA. These suppressive effects of IFN-gamma provide evidence for an additional role of IFN-gamma in regulating GM-CSF production.
Vascular endothelial cells can affect hematopoiesis by releasing granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, we show that GM-CSF production in murine aorta-derived vascular endothelial cells is regulated by two cytokines:interleukin-1 (IL-1), which induces the production of GM-CSF, and interferon gamma (IFN-gamma), which downregulates this production. The GM-CSF gene is constitutively transcribed in these cells and the transcription rate of the GM-CSF gene does not change with either IL-1 alone or IL-1 plus IFN-gamma. Whereas IL-1 treatment increases the GM-CSF mRNA half-life, simultaneous treatment with IL-1 plus IFN-gamma results in a decrease in the mRNA half-life. IL-1 also enhances IL-6 mRNA accumulation in these cells, although by increasing its transcription rate. In this case, IFN-gamma does not affect IL-6 mRNA expression. These data suggest that IL-1-induced GM-CSF expression in endothelial cells is regulated at the posttranscriptional level and that IFN-gamma specifically inhibits GM-CSF expression via destabilization of the mRNA. These suppressive effects of IFN-gamma provide evidence for an additional role of IFN-gamma in regulating GM-CSF production.