Multiple mechanisms control the expression of granulocyte-macrophage colony-stimulating factor by human fibroblasts

Stephen D Nimer, M. J. Gates, H. P. Koeffler, J. C. Gasson

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2374-2377
Number of pages4
JournalJournal of Immunology
Volume143
Issue number7
StatePublished - Jan 1 1989
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

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