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.
Gusella
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GL
Biological Carcinogenesis Development Program, National Cancer Institute-Frederick Cancer Research Facility, MD 21701-1013.
Ayroldi
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Espinoza-Delgado
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I
Varesio
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L
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D015536:Down-Regulation; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016186:Receptor, Macrophage Colony-Stimulating Factor; D011994:Recombinant Proteins; D014158:Transcription, Genetic / Q000187:drug effects; D015291:Transforming Growth Factors / Q000235:genetics
D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015291:Transforming Growth Factors; D007371:Interferon-gamma; D016186:Receptor, Macrophage Colony-Stimulating Factor