1531307

pubmed:Citation

4

Macrophage colony-stimulating factor (M-CSF) is required for the proliferation, differentiation, and activation of monocytes. High-affinity receptors for M-CSF are encoded by the c-fms proto-oncogene. In the present study, we show that c-fms transcripts are detectable in human THP-1 myeloid leukemia cells. Furthermore, radiolabeled 125I-M-CSF is rapidly internalized into THP-1 cells and then degraded intracellularly. The results also show that treatment of THP-1 cells with M-CSF is associated with the activation of protein kinase C (PKC) and the induction of tumor necrosis factor (TNF) gene expression. TNF transcript levels were low to undetectable in uninduced THP-1 cells, reached maximal levels by 1 hour of exposure to M-CSF, and returned to those of control cells by 24 hours. Transcriptional run-on analysis showed that a low level of TNF transcription is detectable in untreated THP-1 cells, and M-CSF treatment increased the rate of TNF transcription. Pretreatment of THP-1 cells with pertussis toxin inhibited the increase in PKC activity but not the induction of TNF transcripts by M-CSF. Moreover, exposure of THP-1 cells to inhibitors of protein kinase activity blocked the increase in TNF messenger RNA. These findings suggest that at least two M-CSF-mediated signaling pathways exist in THP-1 cells and that the induction of TNF may be regulated by a protein kinase-dependent mechanism distinct from PKC.

eng

AIM

MEDLINE

0006-4971

Print

79

NLM

904-12

pubmed-meshheading:1531307-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, pubmed-meshheading:1531307-Biotin, pubmed-meshheading:1531307-Enzyme Activation, pubmed-meshheading:1531307-Flow Cytometry, pubmed-meshheading:1531307-Gene Expression, pubmed-meshheading:1531307-Gene Expression Regulation, pubmed-meshheading:1531307-Humans, pubmed-meshheading:1531307-Isoquinolines, pubmed-meshheading:1531307-Leukemia, Myelomonocytic, Acute, pubmed-meshheading:1531307-Macrophage Colony-Stimulating Factor, pubmed-meshheading:1531307-Pertussis Toxin, pubmed-meshheading:1531307-Piperazines, pubmed-meshheading:1531307-Protein Kinase C, pubmed-meshheading:1531307-Protein Kinase Inhibitors, pubmed-meshheading:1531307-RNA, Messenger, pubmed-meshheading:1531307-Receptor, Macrophage Colony-Stimulating Factor, pubmed-meshheading:1531307-Transcription, Genetic, pubmed-meshheading:1531307-Tumor Cells, Cultured, pubmed-meshheading:1531307-Tumor Necrosis Factor-alpha, pubmed-meshheading:1531307-Virulence Factors, Bordetella

Functional expression of the macrophage colony-stimulating factor receptor in human THP-1 monocytic leukemia cells.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't