Lipopolysaccharide, but not IFN-gamma, down-regulates c-fms mRNA proto-oncogene expression in murine macrophages

In the present study we analyzed the effects of two macrophage activators, bacterial LPS and IFN-gamma, on the expression of the c-fms proto-oncogene in the immortalized murine macrophage cell line ANA-1. ANA-1 cells constitutively expressed significant levels of c-fms mRNA. LPS stimulation induced down-regulation of the expression of c-fms mRNA. In contrast, IFN-gamma did not change c-fms expression. Combined treatment of ANA-1 with IFN-gamma plus LPS resulted in a decrease in c-fms mRNA greater than that induced by LPS alone. Nuclear runoff experiments demonstrated that the down-regulation of c-fms mRNA by LPS or LPS plus IFN-gamma was controlled at a transcriptional level. Moreover, experiments in which c-fms mRNA expression was evaluated after the block of RNA or of protein synthesis did not reveal any difference in c-fms mRNA stability in LPS-treated and in untreated cells. These results demonstrate that LPS does not affect the stability of c-fms mRNA, but it decreases the transcription of the gene.