Human granulocyte-macrophage colony-stimulating factor (GM-CSF) has in vitro and in vivo effects on hemopoiesis and enhances the function of circulating mature meyeoid cells. Unstimulated fibroblasts show low level GM-CSF transcription but no accumulation of GM-CSF mRNA or protein, whereas fibroblasts stimulated by TNF-α, IL-1, and phorbol diester have been shown to produce and secrete GM-CSF. To determine the mechanisms controlling the expression of GM-CSF in human fibroblasts, we used a transient transfection assay to look at the first effect of TNF-α, IL-1, and phorbol diester on GM-CSF promotor sequences. Our results demonstrate that the phorbol diester, 12-O-tetradecanoylphorbol 13-acetate, can stimulate GM-CSF transcription via sequences located within 53 bp upstream of the GM-CSF cap site. TNF-α and IL-1 had no effect on GM-CSF transcription, suggesting that these cytokines act predominantly post-transcriptionally to stimulate production of GM-CSF. Our results demonstrate that multiple mechanisms can be used by human fibroblasts to produce GM-CSF in response to various inflammatory stimuli.
|Number of pages||4|
|Journal||Journal of Immunology|
|State||Published - Jan 1 1989|
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