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Gene Review

CSF2  -  colony stimulating factor 2 (granulocyte...

Homo sapiens

Synonyms: CSF, Colony-stimulating factor, GM-CSF, GMCSF, Granulocyte-macrophage colony-stimulating factor, ...
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Disease relevance of CSF2


Psychiatry related information on CSF2


High impact information on CSF2


Chemical compound and disease context of CSF2


Biological context of CSF2

  • Interleukin 3 (encoded by the IL3 gene) and granulocyte-macrophage colony-stimulating factor (encoded by the CSF2 gene) are small secreted polypeptides that bind to specific cell surface receptors and regulate the growth, gene expression, and differentiation of many of the hematopoietic cell lineages, particularly nonlymphoid cells [21].
  • The IL3 and CSF2 genes have been cloned and mapped to human chromosome bands 5q23-31 [21].
  • Multipoint linkage analysis permits the placement of the region containing the IL3 and CSF2 structural genes on the recombination-genetic linkage map of chromosome 5q and thereby allows the role of these genes in leukemogenesis to be more critically examined [21].
  • Although the levels of expression of the CSF2 and FMS genes remained unaltered, the KRAS2 oncogene was overexpressed approximately six-fold in bone marrow cells from the MDS patient compared with normal donors [22].
  • Novel single nucleotide polymorphisms of the human colony-stimulating factor 2 (CSF2) gene identified by sequencing the entire gene [23].

Anatomical context of CSF2

  • Interleukin-3 (IL3) and granulocyte/macrophage colony-stimulating factor (CSF2) stimulate proliferation and differentiation of various hemopoietic cell types [24].
  • When stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), monocytes yield DCs [25].
  • The participation of contaminant T cells in the observed expression of the GM-CSF gene is excluded because CD16 ligands do not stimulate T cells and CD3 ligands, powerful stimulators of T cells, are inactive on NK cells [26].
  • GM-CSF was precipitated from the supernatant fluids of NK cells stimulated with PDBu/A23187 and its biological activity was demonstrated by the ability of the supernatants to sustain proliferation of the TALL-101 cell line or CML blasts [26].
  • Functional NF-IL6/CCAAT enhancer-binding protein is required for tumor necrosis factor alpha-inducible expression of the granulocyte colony-stimulating factor (CSF), but not the granulocyte/macrophage CSF or interleukin 6 gene in human fibroblasts [27].

Associations of CSF2 with chemical compounds

  • Maximal accumulation of GM-CSF mRNA is observed after PDBu/A23187 stimulation [26].
  • IL 3 and GM-CSF possessed significant histamine-releasing activity in 8 of 10 and 12 of 14 subjects, respectively [28].
  • Other proteins of 150, 125, 63, 55, 42, and 36 Kd were also phosphorylated on tyrosine in response to both GM-CSF and IL-3, although to a lesser degree [29].
  • Optimal expression of IL-12 mRNA and bioactivity in vitro requires specific priming of monocytes by interferon-gamma (IFN-gamma) or granulocyte-macrophage colony-stimulating factor (GM-CSF) before lipopolysaccharide (LPS) stimulation [5].
  • GM-CSF transcripts were induced only by the combination of TNF and EGF [30].

Physical interactions of CSF2

  • These data support the hypothesis that IL-6 may have a direct effect on myeloid hematopoietic progenitor cells, and that GM-CSF interacts synergistically with IL-6 by acting on the same target cells [31].
  • This competition occurred at 37 degrees C as well as 4 degrees C. Low affinity GM-CSF binding was not affected by IL-3 [32].
  • Cross-linking experiments on HL-60 cells demonstrated two IL-5-containing complexes of Mr 150,000 and Mr 80,000 both of which were inhibited by GM-CSF [33].
  • Experimental findings suggest that granulocyte-monocyte-colony stimulating factor (GM-CSF) synergistically interacts with interleukin-2 (IL-2) in generating an efficient antigen-specific immune response [34].
  • GM-CSF mRNA expression showed the same pattern of response to these cytokines, indicating transcriptional or pre-transcriptional regulation, and there was no evidence that IFN-gamma was acting by destabilizing GM-CSF mRNA [35].

Enzymatic interactions of CSF2


Co-localisations of CSF2

  • High level expression of CD1b in MS lesions was found to colocalize with the presence of GM-CSF in astrocytes [41].

Regulatory relationships of CSF2

  • Target genes known to be transcriptionally activated by TNF-alpha include the granulocyte (G)-colony-stimulating factor (CSF) gene, the granulocyte/macrophage (GM)-CSF gene, as well as the interleukin (IL) 6 gene [27].
  • Finally, the importance of IL-6 in monocytopoiesis was demonstrated in serum-deprived bone marrow cultures: addition of exogenous IL-6 to cultures stimulated with GM-CSF resulted in increased numbers of monocytic colonies [42].
  • Our data indicate that IL-10 profoundly inhibits the autonomous growth of CMML cells in vitro most likely through suppression of endogenous GM-CSF release [43].
  • As the same beta c subunit also forms high-affinity receptors for IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) with the respective cytokine-specific alpha subunit, the expression of the alpha subunits is responsible for specificity of cytokines [44].
  • IL-8 secretion by monocytes was stimulated within 2 hours after incubation with rhGM-CSF or rhIL-3 [45].

Other interactions of CSF2

  • Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors [46].
  • Instead, complexes activated by IL-3 or GM-CSF contained a tyrosine-phosphorylated protein of 80 kilodaltons [47].
  • The effect of GM-CSF on HLA-DR was not mediated by the generation of IFN-gamma in vitro because it was not blocked by anti-IFN-gamma mAb [48].
  • Because we have recently reported that supernatants of cultured RA synovial cells produce a non-IFN-gamma factor that induces HLA-DR on monocytes, we then attempted to neutralize this factor with specific anti-GM-CSF mAb [48].
  • GM-CSF also increased HLA-DR mRNA expression and surface HLA-DQ expression, but decreased CD14 (a monocyte/macrophage antigen) expression [48].

Analytical, diagnostic and therapeutic context of CSF2

  • Linkage mapping of the human CSF2 and IL3 genes [21].
  • Whether previously described HRFs relate specifically to IL 3 or GM-CSF must await primary sequence analysis of HRF and/or studies with monospecific antisera [28].
  • Using specific enzyme-linked immunosorbent assays (ELISAs) and Northern analysis, GM-CSF and G-CSF expression were followed in human synovial fibroblast-like cells in response to a number of agents, either alone or in the presence of an optimal stimulatory concentration of interleukin-1 (IL-1) [49].
  • In response to both adhesion and recombinant human GM-CSF (rhGM-CSF) stimulation for 120 hours, radioimmunoassays and bioassays showed that cord MNCs produced twofold to threefold less M-CSF protein compared with adult MNCs [50].
  • Northern blot analysis also showed a fourfold decrease in M-CSF mRNA expression in both unstimulated and GM-CSF-induced cord versus adult MNCs [50].


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  20. Interleukin 3 and granulocyte/macrophage-colony-stimulating factor render human basophils responsive to low concentrations of complement component C3a. Bischoff, S.C., de Weck, A.L., Dahinden, C.A. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  21. Linkage mapping of the human CSF2 and IL3 genes. Frolova, E.I., Dolganov, G.M., Mazo, I.A., Smirnov, D.V., Copeland, P., Stewart, C., O'Brien, S.J., Dean, M. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  22. KRAS2 oncogene overexpression in myelodysplastic syndrome with translocation 5;12. Srivastava, A., Boswell, H.S., Heerema, N.A., Nahreini, P., Lauer, R.C., Antony, A.C., Hoffman, R., Tricot, G.J. Cancer Genet. Cytogenet. (1988) [Pubmed]
  23. Novel single nucleotide polymorphisms of the human colony-stimulating factor 2 (CSF2) gene identified by sequencing the entire gene. Kajita, M., Iwasaki, H., Ota, N., Shinohara, Y., Kodaira, M., Nakajima, T., Emi, M. J. Hum. Genet. (2001) [Pubmed]
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  27. Functional NF-IL6/CCAAT enhancer-binding protein is required for tumor necrosis factor alpha-inducible expression of the granulocyte colony-stimulating factor (CSF), but not the granulocyte/macrophage CSF or interleukin 6 gene in human fibroblasts. Kiehntopf, M., Herrmann, F., Brach, M.A. J. Exp. Med. (1995) [Pubmed]
  28. Human recombinant granulocyte-macrophage colony-stimulating factor and interleukin 3 cause basophil histamine release. Haak-Frendscho, M., Arai, N., Arai, K., Baeza, M.L., Finn, A., Kaplan, A.P. J. Clin. Invest. (1988) [Pubmed]
  29. Signal transduction of the human granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors involves tyrosine phosphorylation of a common set of cytoplasmic proteins. Kanakura, Y., Druker, B., Cannistra, S.A., Furukawa, Y., Torimoto, Y., Griffin, J.D. Blood (1990) [Pubmed]
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  31. Human interleukin-6 supports granulocytic differentiation of hematopoietic progenitor cells and acts synergistically with GM-CSF. Caracciolo, D., Clark, S.C., Rovera, G. Blood (1989) [Pubmed]
  32. Common binding structure for granulocyte macrophage colony-stimulating factor and interleukin-3 on human acute myeloid leukemia cells and monocytes. Budel, L.M., Elbaz, O., Hoogerbrugge, H., Delwel, R., Mahmoud, L.A., Löwenberg, B., Touw, I.P. Blood (1990) [Pubmed]
  33. Interleukin-5, interleukin-3, and granulocyte-macrophage colony-stimulating factor cross-compete for binding to cell surface receptors on human eosinophils. Lopez, A.F., Vadas, M.A., Woodcock, J.M., Milton, S.E., Lewis, A., Elliott, M.J., Gillis, D., Ireland, R., Olwell, E., Park, L.S. J. Biol. Chem. (1991) [Pubmed]
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