Involvement of immediate-early gene expression in the synergistic effects of steel factor in combination with granulocyte-macrophage colony-stimulating factor or interleukin-3 on proliferation of a human factor-dependent cell line.

Steel factor (SLF) synergizes with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) to stimulate proliferation of human factor-dependent cell line, MO7e. To elucidate molecular mechanisms underlying this synergism, induction of immediate-early genes was studied. Treatment of MO7e cells with SLF, GM-CSF, and IL-3 induced/enhanced expression of c-fos, junB, egr-1, and c-myc genes. SLF treatment of MO7e cells led to higher expression of c-fos, junB, and egr-1 genes than did treatment with GM-CSF or IL-3. However, GM-CSF and IL-3 had more prolonged effects on enhancement of the c-myc gene than SLF. Using optimal dosages for cell proliferation, induction of c-fos and junB was greater than additive with SLF plus GM-CSF or IL-3, as compared with each factor alone. Using suboptimal amounts of SLF with optimal GM-CSF or IL-3, induction of c-fos, junB, egr-1, and c-myc genes was greater than additive. De novo protein synthesis was not required for greater induction of these immediate-early genes by the combination of SLF plus GM-CSF. Based on nuclear run-on and actinomycin D experiments, the data suggest that the synergistic effects of SLF plus GM-CSF on the induction of immediate-early genes may be mediated in part at the level of transcription and mRNA stabilization for c-fos, at the level of mRNA stabilization for junB, and at the level of transcription for egr-1.