Interferon-gamma destabilizes interleukin-1-induced granulocyte-macrophage colony-stimulating factor mRNA in murine vascular endothelial cells.
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.
Akahane
K
K
Division of Cytokine Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892.
Pluznik
D H
DH
D000818:Animals; D001011:Aorta; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004355:Drug Stability; D004730:Endothelium, Vascular / Q000378:metabolism*; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006207:Half-Life; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism*; D011994:Recombinant Proteins; D014158:Transcription, Genetic
D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003609:Dactinomycin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor