Production of macrophage colony-stimulating factor (M-CSF) by human monocytes is differentially regulated by GM-CSF, TNF alpha, and IFN-gamma.
Macrophage colony-stimulating factor (M-CSF) stimulates the survival, proliferation, and differentiation of mononuclear phagocytes. In this study, the qualitative and relative quantitative ability of various cytokines to induce and to synergize in M-CSF production by monocytes was studied. GM-CSF and the phorbolester PMA were strong inducers of M-CSF m-RNA expression. This was correlated closely with the secretion of M-CSF protein as measured in the murine M-NFS-60 cell line bioassay. Both TNF alpha and IFN-gamma enhanced M-CSF message levels induced by GM-CSF, but only TNF alpha synergized with GM-CSF in the induction of M-CSF protein secretion. M-CSF transcripts induced by TNF alpha and IFN-gamma were much lower compared to those induced by GM-CSF and PMA and were not accompanied by the secretion of M-CSF protein. In addition, costimulation of cells with TNF alpha and IFN-gamma did not result in M-CSF production. Although M-CSF did not induce its own message, it further enhanced M-CSF transcripts induced by GM-CSF. LPS also failed to induce M-CSF message or secretion. These results show that cytokines differ in their ability to induce or to synergize in the induction of biologically active M-CSF protein. They further demonstrate that M-CSF message expression, induced by cytokines, does not always correlate with M-CSF protein secretion.
Gruber
M F
MF
Division of Cytokine Biology, Food and Drug Administration, Bethesda, Maryland 20892.
Gerrard
T L
TL
D002460:Cell Line; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D010703:Phorbol Esters; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor