Gene-expression and release of macrophage-colony stimulating factor in quiescent and proliferating fibroblasts. Effects of serum, fibroblast growth-promoting factors, and IL-1.

Macrophage (M)-CSF induces the proliferation and differentiation of macrophage-precursor cells, and is an important factor in the survival and activation of mature mononuclear phagocytes. Several effector cell populations such as mononuclear phagocytes, endothelial cells, and fibroblasts, have been reported to produce M-CSF at high levels. We investigated the gene-expression and release of M-CSF in fibroblasts. Quiescent, growth-arrested, fibroblasts showed little expression of M-CSF as demonstrated by Northern blot analysis, and little production of M-CSF as measured in the murine bone marrow bioassay. Initiation of proliferation of fibroblasts by fetal bovine serum was followed by an increase in M-CSF transcription and release of the protein. Similarly, single factors (platelet-derived growth factor) or combinations of factors (epidermal growth factor (EGF) + insulin, platelet-derived growth factor + EGF + insulin, or fibroblast growth factor + EGF + insulin) that induced proliferation of the fibroblasts, also induced increased expression of M-CSF. As soon as 1 h after the addition of fetal bovine serum, M-CSF expression was increased, and reached a plateau at 2 to 8 h after induction. IL-1 increased M-CSF expression both in quiescent and proliferating fibroblasts, and induced the expression and release of granulocyte-, and granulocyte/macrophage-CSF. These results show that expression of M-CSF in fibroblasts is not constitutively at a high level, but undergoes regulation depending on the cellular proliferative state and on further activation by acute response proteins such as IL-1.