Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human myeloid cell line HL-60 expresses approximately 300 high-affinity granulocyte-macrophage colony-stimulating factor receptors (GM-CSFRs), yet treatment of these cells with GM-CSF does not result in enhanced cellular proliferation or increases in protein tyrosine phosphorylation. In contrast, GM-CSF induces rapid increases in protein tyrosine phosphorylation and proliferative responses in HL-60 cells pretreated for 3 days in dimethyl sulfoxide (DMSO). Similarly, HL-60 cells pretreated with retinoic acid or 1,25 dihydroxyvitamin D3 were also capable of responding to GM-CSF. Interestingly, each of these treatments resulted in increased expression of the src-like tyrosine kinase hck. Stimulation with GM-CSF increased hck autophosphorylation in DMSO-treated HL-60 cells, suggesting that hck is a component of the GM-CSF signal transduction pathway. To determine if hck has a role in the DMSO-induced recoupling of the GM-CSFR, we overexpressed hck in HL-60 cells. The resulting cell line (HL-60/hck) expresses hck mRNA and protein at levels comparable with DMSO-treated HL-60 cells. Stimulation of HL-60/hck cells with GM-CSF results in activation of hck, increases in protein tyrosine phosphorylation, and increased proliferation. These results show that cytokine receptors can exist in an uncoupled form and suggest that in HL-60 cells, appropriate levels of the src-like tyrosine kinase hck are critical for functional coupling of the GM-CSFR to biologic responses.
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PMID:Hck expression correlates with granulocyte-macrophage colony-stimulating factor-induced proliferation in HL-60 cells. 801 33

Homeobox proteins comprise a major class of transcription factors, which have been implicated in normal hematopoiesis and leukemogenesis. Notable in this context is the homeobox gene HOX-B8 (formerly known as HOX-2.4), which was shown to cooperate with hematokines to induce leukemia, and to enhance self-renewal of immature myeloid progenitors when expressed alone. How HOX-B8 may affect lineage specific development of hematopoietic progenitor cells is unknown. Here it is shown that ectopic expression of HOX-B8 specifically inhibited dimethyl sulfoxide (DMSO)-induced granulocytic differentiation of autonomously proliferating HL-60 myeloid progenitor cells. HOX-B8 also inhibited the granulocyte colony-stimulating factor (G-CSF)-induced granulocytic developmental program of factor dependent 32Dcl3 hematopoietic progenitors, including survival, proliferation, and differentiation, as evident by rapid apoptosis of the cells following removal of interleukin-3 (IL-3) and addition of G-CSF. In sharp contrast, HOX-B8 had no effect on macrophage differentiation of M1 and HL-60 cells induced by IL-6 and phorbol-12-myristate-13-acetate, respectively. Moreover, HOX-B8 expression endowed the 32Dcl3 cells with the ability to be induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) for terminal differentiation exclusively along the macrophage lineage; this effect was at least partially mediated via expression of the zinc finger transcription factor Egr-1. Thus, ectopic expression of HOX-B8 in hematopoietic progenitor cells appears to differentially affect lineage specific development, negatively regulating granulocyte development and positively regulating macrophage development.
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PMID:Lineage-specific regulation of hematopoiesis by HOX-B8 (HOX-2.4): inhibition of granulocytic differentiation and potentiation of monocytic differentiation. 929 16

A new method for an assay of human granulocyte colony-stimulating factor (hG-CSF) has been developed using human promyelocytic HL-60 cells. The proliferation of HL-60 cells had been suppressed by the addition of dimethyl sulfoxide (DMSO) or retinoic acid (RA). These differentiating agent-treated HL-60 cells exhibited an increase in their number in response to recombinant hG-CSF (rhG-CSF). Neither dibutyl-cAMP nor interferon-gamma (IFN-gamma)-treated HL-60 cells, however, showed an increase in their number in response to rhG-CSF. The proliferation rate of DMSO-pretreated HL-60 cells was linearly increased from 0.3 to 10 ng/ml of rhG-CSF. L-Value of HL-60 cells assay was 0.027 +/- 0.012. The activities of non-glycosylated rhG-CSF produced by Escherichia coli and glycosylated rhG-CSF produced by chinese hamster ovary (CHO) cells were compared using DMSO-treated HL-60 cells; no significant difference between them. DMSO-treated HL-60 cells also responded to interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), but did not respond to erythropoietin or macrophage colony-stimulating factor, suggesting that the responsiveness of these cells to growth factor is restricted to myelogenic cytokines. In conclusion, DMSO- or RA-treated HL-60 cells are useful for the measurement of bioactivity of hG-CSF.
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PMID:Bioassay of human granulocyte colony-stimulating factor using human promyelocytic HL-60 cells. 933 73

Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces the proliferation and maturation of immature myeloid progenitor cells and primes mature cell function in phagocytes. To investigate whether the biochemical events following the binding of GM-CSF to its receptor are differentiation dependent we analysed GM-CSF mediated activation of the JAK 2-STAT 5 and MAP kinase pathways in undifferentiated HL-60 cells and HL-60 cells induced to differentiate with dimethyl sulphoxide (DMSO) or retinoic acid (RA). GM-CSF stimulated MAP kinase activation in both the undifferentiated and differentiated HL-60 cells. Activation of MAP kinase (expressed as a proportion of total cellular MAP kinase) was maximal at 5 min and of similar magnitude in both cell types. There was, however, a marked difference in the later kinetics of activation, with the response being transient in the undifferentiated cells and disappearing within 15 min, whereas it was prolonged and persisted for at least 60 min in the differentiated cells. GM-CSF mediated activation of STAT 5 was markedly increased (15-20-fold) after differentiation of HL-60 cells but the kinetics of activation did not change. The increase in STAT 5 activation was not due to a change in total cellular STAT 5 expression but correlated with increased JAK-2 protein levels. These data show that in the HL-60 cell model, differentiation modulates the activation of signalling molecules downstream of the GM-CSF receptor.
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PMID:Differentiation-linked changes in granulocyte-macrophage colony-stimulating factor receptor mediated signalling in the HL-60 promyelocytic cell line. 957 87

Identification of tumor-associated antigens (TAAs) and their class I MHC-restricted epitopes now allows for the rational design of peptide-based cancer vaccines. A biocompatible system capable of sustained release of biologically relevant levels of cytokine and TAA peptide could provide a more effective microenvironment for antigen presentation. Our goal was to test a sustained-release cytokine/TAA peptide-based formulation using a highly purified polysaccharide [poly-N-acetyl glucosamine (p-GlcNAc)] polymer. Granulocyte-macrophage colony-stimulating factor (GM-CSF; 100 microgram) and MART-1(27-35) peptide (128 microgram in DMSO) were formulated into p-GlcNAc. Peptide release was assayed in vitro using interleukin 2 production from previously characterized MART-1(27-35)-specific Jurkat T cells (JRT22). GM-CSF release was assayed via ELISA and proliferation of M-07e (GM-CSF-dependent) cells. Local bioavailability of MART-1(27-35) peptide for uptake and presentation by antigen-presenting cells was demonstrated for up to 6 days (>0.5 microgram/ml). More than 1.0 microgram/ml GM-CSF was concomitantly released over the same period. Biocompatibility and local tissue response to p-GlcNAc releasing murine GM-CSF was determined in C57BL/6 mice via s.c. injection using murine GM-CSF (0. 2 microgram/ml) in 200 microliter of a 2.5% polymer gel. Significant lymphocytic and eosinophilic infiltration was observed 2-7 days after injection with polymer containing murine GM-CSF. The results of our studies show that this biocompatible system is capable of a sustained concomitant release of biologically active peptide and cytokine into the local microenvironment. These findings support further studies to validate a p-GlcNAc delivery system vehicle for a cytokine/TAA peptide-based cancer vaccine.
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PMID:Characterization of a sustained-release delivery system for combined cytokine/peptide vaccination using a poly-N-acetyl glucosamine-based polymer matrix. 981 61


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