IL-2 enhances c-fms expression in human monocytes.
We investigated the effects of IL-2 and IFN-gamma on the expression of the proto-oncogene c-fms mRNA, which encodes for the macrophage CSF receptor. Low constitutive expression of c-fms mRNA was detected in fresh human monocytes. Stimulation of monocytes with IL-2 induced a significant increase in c-fms mRNA relative to medium control that was observed as early as 6 h after IL-2 stimulation. Dose-response experiments showed that 100 U/ml of IL-2 were sufficient to enhance the expression of c-fms mRNA. In contrast, IFN-gamma did not modify the levels of c-fms transcript. Immunoprecipitation experiments demonstrated that IL-2 enhanced c-fms glycoprotein levels. Experiments in which monocytes were activated with IFN-gamma or IL-2 followed by macrophage CSF-1 and then tested for tumoricidal activity demonstrated that macrophage CSF-1 sustained the cytotoxic activity induced by IL-2 but not by IFN-gamma. These data demonstrate that IL-2 enhances c-fms mRNA and c-fms glycoprotein expression suggesting that IL-2, by augmenting expression of macrophage CSF-1 receptors, can lead to prolongation of monocyte-mediated tumoricidal activity obtained in the presence of exogenous macrophage CSF-1.
Espinoza-Delgado
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Division of Cancer Treatment, National Cancer Institute (NCI), Frederick, MD 21701-1013.
Longo
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Gusella
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Varesio
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D003115:Colony-Stimulating Factors / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D016186:Receptor, Macrophage Colony-Stimulating Factor
D003115:Colony-Stimulating Factors; D007376:Interleukin-2; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016186:Receptor, Macrophage Colony-Stimulating Factor