Epidermal growth factor stimulates macrophage colony-stimulating factor (M-CSF) mRNA expression and M-CSF release in cultured murine stromal cells

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Abstract
Macrophage colony-stimulating factor (M-CSF) released by stromal cells of the bone marrow microenvironment plays a crucial role in the growth and proliferation of mononuclear cells. Several peptide mitogens including interleukin-1, tumour necrosis factor, platelet-derived growth factor and fibroblast growth factor stimulate the release of M-CSF and may be important in mediating the haematopoietic response to inflammation. Epidermal growth factor (EGF), released from platelets during aggregation, is mitogenic for a variety of cell types and may cause the release of certain cytokines. In this study we used the TC-1 murine stromal cells which constitutively secrete M-CSF as a model to study the regulation of M-CSF in response to EGF. EGF markedly stimulated the steady state expression of M-CSF mRNA with a peak effect observed at 3 h. This was associated with the release of M-CSF protein as determined by radioimmunoassay. EGF also stimulated DNA synthesis in a concentration dependent manner. Although TC-1 cells express GM-CSF mRNA, this was not induced by EGF. These findings suggest that EGF is a key regulatory molecule for M-CSF and may indirectly effect haematopoiesis via the release of M-CSF from stromal cells.