Lipopolysaccharide-inducible macrophage early genes are induced in Balb/c 3T3 cells by platelet-derived growth factor.

We have previously described the isolation and characterization of a set of cDNA clones encoding lipopolysaccharide (LPS)-induced early genes in murine peritoneal macrophages. The treatment of macrophages with LPS also stimulates the expression of four early or competence genes (c-fos, c-myc, JE, and KC) described in platelet-derived growth factor-stimulated Balb/c 3T3 cells. These latter findings led to the hypothesis that long term, adaptive responses such as DNA synthesis in fibroblasts and functional activation of macrophages may share multiple mechanistic pathways. To test this possibility, we have examined the expression of four LPS-inducible macrophage genes in platelet-derived growth factor-stimulated Balb/c 3T3 fibroblasts. The results demonstrate that three of these four genes are expressed in 3T3 cells in a fashion reminiscent of other growth factor-stimulated competence genes. All three mRNAs are expressed even in the presence of cycloheximide and two of the three exhibit superinducibility. The accumulation of these specific mRNA species was dependent upon the stimulation of transcription as determined by nuclear "run-off" studies. The platelet-derived growth factor dose dependence is comparable both for stimulation of DNA synthesis and expression of the three early genes. Furthermore, expression of all three genes preceded the entry of the cells into S phase, suggesting an association with cell cycle entry. Stimulation of 3T3 cells with epidermal growth factor resulted in DNA synthesis but not early gene expression. This latter result indicates that these early gene products are not necessary for 3T3 cell mitogenesis. Nevertheless, the expression of these genes in two different cell types in association with two distinct functional responses suggests that they contribute common functions either in terms of the physiologic response in which these cells participate (e.g. inflammation) or in the regulatory mechanisms which govern such responses.