Several cytokines and mitogens can induce various cells to express the granulocyte macrophage colony stimulating factor (GM-CSF) gene, whereas other cytokines antagonize the expression of GM-CSF. Previously we reported that interleukin-1 (IL-1) induces GM-CSF gene expression in B cell lines, while interleukin-4 (IL-4) inhibits this induced expression. To further explore whether the inhibition of IL-1 induced GM-CSF is limited to IL-4, we used vascular endothelial cells which can affect hematopoiesis by releasing GM-CSF. In the present study, we show that GM- CSF production in murine aorta-derived vascular endothelial cells is also regulated by two cytokines, in a way similar to B cells. However, while in B cells IL-4 antagonizes the activity of Il-1 it does not do so in endothelial cells. We found that another cytokine, interferon-gamma (IFNgamma), is capable of downregulating the production of GM-CSF. The GM-CSF is constitutively transcribed in endothelial 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 interleukin-6 (IL-6) mRNA accumulation in these cells 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 data show that while IL-1 is capable of inducing GM-CSF gene expression in various cell types such as in B cell lines and endothelial cells, the downregulation of this activity by IL-4 and INF-gamma is more limited and is dependent on the cell type.
