Colony-stimulating factor induction of protooncogene expression in rat alveolar macrophages.
The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on the expression of c-fos and c-myc protooncogenes was studied in rat alveolar macrophages (AM). AM were exposed in vitro to GM-CSF (100 U/ml) or M-CSF (1,000 U/ml) for 30-120 min, and c-fos and c-myc mRNA expression was determined by in situ hybridization and Northern blot analysis. GM-CSF caused a rapid induction of c-fos mRNA after 30 min and c-myc mRNA after 60 min. Exposure to M-CSF stimulated maximal expression of c-fos mRNA after 60 min and c-myc mRNA after 120 min. Under the same experimental conditions lipopolysaccharide (100 ng/ml) induced a comparable amount of c-fos and c-myc mRNA expression, whereas culture of AM with medium alone did not induce c-fos or c-myc expression. Thus GM-CSF and M-CSF induce AM in vitro to express the nuclear protooncogenes c-fos and c-myc. This effect of colony-stimulating factors on protooncogene expression may be of importance in the local regulation of AM activation and/or proliferation in an inflammatory lung response.
Schaberg
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Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Filderman
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AE
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D009693:Nucleic Acid Hybridization; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases