CSF-1-induced gene expression in macrophages: dissociation from the mitogenic response.
Early gene expression associated with the mitogenic response to colony stimulating factor-1 (CSF-1) has been examined in BAC1.2F5, a CSF-1-dependent murine macrophage cell line. Stimulation of arrested cells by CSF-1 resulted in acute, transient elevation in c-fos and subsequently in c-myc mRNA levels. Dramatic, sustained elevations were observed for JE and KC mRNAs, which are induced by platelet-derived growth factor (PDGF) in 3T3 cells. The kinetics of expression of all four messages were similar to those reported in PDGF-stimulated fibroblasts, implying a program of gene expression common to these two mitogens. Granulocyte-macrophage CSF (GM-CSF) can replace CSF-1 in stimulating the growth of 2F5 cells. It induced mRNAs for c-fos, c-myc and JE but not KC. Therefore KC expression, although correlated with mitogenesis, is not required for proliferation. The effects of CSF-1 were also examined in cells cycling continuously in its absence: 2F5 cells incubated in GM-CSF and an autonomous variant subclone of 2F5. In either case, the only detected growth effect of CSF-1 was a reduction in doubling-time. Nevertheless, all four of the mRNAs induced by CSF-1 in arrested cultures of 2F5 were strongly induced with the same kinetics in these cycling cells. Thus it would appear that the functions mediated by this early-gene program are not restricted to the mitogenic stimulation of arrested cells.
D000818:Animals; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000502:physiology*; D007700:Kinetics; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D051379:Mice; D009693:Nucleic Acid Hybridization; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics*; D014158:Transcription, Genetic
D003115:Colony-Stimulating Factors; D012333:RNA, Messenger