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Gene Review

IL3  -  interleukin 3

Homo sapiens

Synonyms: Hematopoietic growth factor, IL-3, Interleukin-3, MCGF, MGC79398, ...
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Disease relevance of IL3

  • Hemorrhage occurred in approximately 40% in all arms, whereas infection rates were higher in the granulocyte/macrophage colony stimulating factor (GM-CSF)- or IL3-containing arm [1].
  • Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis [2].
  • Southern blot analysis of somatic cell hybrids retaining the normal or the deleted chromosome 5 from two patients with the refractory anemia 5q- syndrome indicated that IL-3 sequences were absent form the hybrids retaining the deleted chromosome 5 but not from hybrids that had a cytologically normal chromosome 5 [3].
  • The degranulation of eosinophils induced by GM-CSF, IL-5, and IL-3 may have relevance to the potential clinical toxicity of these hematopoietins, which also stimulate eosinophilopoiesis [4].
  • In summary, gibbon IL-3 is a growth factor that can synergize with other CSFs to enhance proliferation of myeloid-committed progenitors, suggesting that combinations of CSFs may have clinical utility in patients with neutropenia of various etiologies [5].

Psychiatry related information on IL3


High impact information on IL3


Chemical compound and disease context of IL3


Biological context of IL3

  • Flow cytometric analysis of cells harvested from cultures of X-irradiated cells stimulated with thrombopoietin plus IL3 showed no significant differences in the expression of surface antigens and DNA ploidy distribution of megakaryocytes from the control [16].
  • These mapping results suggest the gene order 5cen-IL3/GMCSF-IL5-IL4-IL9-MCSFR+ ++-qter [17].
  • We conclude that multi-CSF may prove to have important therapeutic potential in vivo as a stimulus for hematopoiesis [18].
  • The functionality of IL-3R was demonstrated by the fact that IL-3 rescued IFN-beta-treated monocytes from apoptosis [19].
  • Tyrosine phosphorylation was dependent on the concentration of GM-CSF over the range of 0.1 to 10 ng/mL and on IL-3 over the range of 1 to 30 ng/mL [20].

Anatomical context of IL3

  • Interleukin-3 (IL3) and granulocyte/macrophage colony-stimulating factor (CSF2) stimulate proliferation and differentiation of various hemopoietic cell types [21].
  • In Ficoll-Isopaque isolated and T cell-depleted ALL bone marrow samples, IL2 (two cases), IL3 (four cases), and GM-CSF (one case) infrequently stimulated DNA synthesis measured by 3H-thymidine (TdR) uptake, and the other recombinant growth factors completely failed to do so [22].
  • We find that IL2 infusion accelerates neutrophil recovery and that granulocyte-macrophage colony stimulating factor (GMCSF) and IL3 mRNA become detectable in circulating mononuclear cells [23].
  • These findings suggest that IL3 plays a key role in promoting the survival of X-irradiated CD34(+) CFU-megakaryocytes from peripheral blood as well as those from cord blood, though the former are more radiosensitive [16].
  • A combination of interleukin 3 (IL3) and erythropoietin (EPO) induces 3 types of day 14 colonies; erythroid burst-forming units (BFU-E, 40 +/- 29/5 X 10(4) BM cells), granulocytes-macrophage colony forming units (CFU-GM, 143 +/- 29/5 X 10(4) cells and mixed colonies (CFU-GEMM, 24 +/- 13/5 X 10(4) cells) [24].

Associations of IL3 with chemical compounds


Physical interactions of IL3

  • IL-3 could also be coimmunoprecipitated with anti-IL-3R alpha or anti-beta c MAB, but it was not covalently attached to the receptor [29].
  • Analysis of mixing experiments and of the morphology of the BFU-E in culture indicated that IL-9 interacts preferentially with a relatively early population of IL-3-responsive BFU-E [30].
  • This report details the crystal structure of the ligand-binding domain of the GM-CSF/IL-3/IL-5 receptor beta-chain (beta(c)) signaling subunit in complex with the Fab fragment of the antagonistic monoclonal antibody, BION-1 [31].
  • We discuss these findings with regard to the stoichiometry, activation, and signalling of the normal GM-CSF/IL-3/IL-5 receptor complexes [32].
  • When IL-3 was connected to Epo by a short linker, the binding affinity of the IL-3 moiety was lower [33].

Enzymatic interactions of IL3

  • CRKL has been shown to be tryosine phosphorylated in response to normal hematopoietic growth factor receptor signaling with ligands such as thrombopoietin, erythropoietin or steel factor [34].
  • Previous studies have shown that SHC proteins are phosphorylated on Y239/Y240 and Y313 (Y317 in humans) by tyrosine kinases such as the EGF and IL3 receptors [35].

Regulatory relationships of IL3

  • In some experiments, IL-3 or IgER activation alone also induced IL-4 production close to the detection limit [25].
  • Proliferation of ELF-153 cells was highly stimulated by interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor and to a lesser extent by stem cell factor and IL-6 [36].
  • SCF also enhanced cell proliferation in the presence of either IL-3 or low concentrations of GM-CSF [37].
  • IL-2 had no effect on megakaryocytes generated from CD34(+) cells stimulated with IL-3 and SCF [38].
  • We show here that human IL-3 induces heterodimerization of IL-3R alpha and beta c and that disulfide linkage of these chains is involved in receptor activation but not high-affinity binding [29].

Other interactions of IL3


Analytical, diagnostic and therapeutic context of IL3


  1. Low-dose cytosine arabinoside (LD-AraC) vs LD-AraC plus granulocyte/macrophage colony stimulating factor vs LD-AraC plus Interleukin-3 for myelodysplastic syndrome patients with a high risk of developing acute leukemia: final results of a randomized phase III study (06903) of the EORTC Leukemia Cooperative Group. Zwierzina, H., Suciu, S., Loeffler-Ragg, J., Neuwirtova, R., Fenaux, P., Beksac, M., Harousseau, J., Nuessler, V., Cermak, J., Solbu, G., Willemze, R., de Witte, T., Amadori, S. Leukemia (2005) [Pubmed]
  2. Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis. Firestein, G.S., Xu, W.D., Townsend, K., Broide, D., Alvaro-Gracia, J., Glasebrook, A., Zvaifler, N.J. J. Exp. Med. (1988) [Pubmed]
  3. The interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q. Le Beau, M.M., Epstein, N.D., O'Brien, S.J., Nienhuis, A.W., Yang, Y.C., Clark, S.C., Rowley, J.D. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  4. Differentiation and functional activity of human eosinophilic cells from an eosinophil HL-60 subline: response to recombinant hematopoietic growth factors. Fabian, I., Lass, M., Kletter, Y., Golde, D.W. Blood (1992) [Pubmed]
  5. Recombinant gibbon interleukin-3 acts synergistically with recombinant human G-CSF and GM-CSF in vitro. Paquette, R.L., Zhou, J.Y., Yang, Y.C., Clark, S.C., Koeffler, H.P. Blood (1988) [Pubmed]
  6. Autografting with peripheral blood stem cells mobilized by sequential interleukin-3/granulocyte-macrophage colony-stimulating factor following high-dose chemotherapy in non-Hodgkin's lymphoma. Haas, R., Ehrhardt, R., Witt, B., Goldschmidt, H., Hohaus, S., Pförsich, M., Ehrlich, H., Färber, L., Hunstein, W. Bone Marrow Transplant. (1993) [Pubmed]
  7. Cytokine production in panic disorder patients. Weizman, R., Laor, N., Wiener, Z., Wolmer, L., Bessler, H. Clinical neuropharmacology. (1999) [Pubmed]
  8. Impaired expression of the thrombopoietin receptor by platelets from patients with polycythemia vera. Moliterno, A.R., Hankins, W.D., Spivak, J.L. N. Engl. J. Med. (1998) [Pubmed]
  9. Altered metabolism of mast-cell growth factor (c-kit ligand) in cutaneous mastocytosis. Longley, B.J., Morganroth, G.S., Tyrrell, L., Ding, T.G., Anderson, D.M., Williams, D.E., Halaban, R. N. Engl. J. Med. (1993) [Pubmed]
  10. Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors. Kitamura, T., Sato, N., Arai, K., Miyajima, A. Cell (1991) [Pubmed]
  11. Hematopoietic growth factor stimulation and cytarabine cytotoxicity in vitro: effects in untreated and relapsed or primary refractory acute myeloid leukemia cells. te Boekhorst, P.A., Löwenberg, B., Sonneveld, P. Leukemia (1994) [Pubmed]
  12. Tumor necrosis factor alpha modulates the messenger RNA expression of hematopoietic growth factor genes in fresh blast cells from patients with acute myeloblastic leukemia. Bergamaschi, G., Cazzola, M., Rosti, V., Carlo-Stella, C., Santini, V., Ponchio, L., Peverali, F.A., Della Valle, G., Rossi Ferrini, P., Ascari, E. Leukemia (1991) [Pubmed]
  13. Effects of flt3 ligand on acute myeloid and lymphocytic leukemic blast cells from children. McKenna, H.J., Smith, F.O., Brasel, K., Hirschstein, D., Bernstein, I.D., Williams, D.E., Lyman, S.D. Exp. Hematol. (1996) [Pubmed]
  14. Inducing and enhancing effects of IL-3, -5, and -6 and GM-CSF on histamine release from human basophils. Miadonna, A., Roncarolo, M.G., Lorini, M., Tedeschi, A. Clin. Immunol. Immunopathol. (1993) [Pubmed]
  15. Diphtheria toxin fused to human interleukin-3 is toxic to blasts from patients with myeloid leukemias. Frankel, A.E., McCubrey, J.A., Miller, M.S., Delatte, S., Ramage, J., Kiser, M., Kucera, G.L., Alexander, R.L., Beran, M., Tagge, E.P., Kreitman, R.J., Hogge, D.E. Leukemia (2000) [Pubmed]
  16. Effects of the combination of thrombopoietin with cytokines on the survival of X-irradiated CD34(+) megakaryocytic progenitor cells from normal human peripheral blood. Kashiwakura, I., Inanami, O., Murakami, M., Takahashi, T.A., Kuwabara, M., Takagi, Y. Radiat. Res. (2002) [Pubmed]
  17. Order of human hematopoietic growth factor and receptor genes on the long arm of chromosome 5, as determined by fluorescence in situ hybridization. Kluck, P.M., Wiegant, J., Raap, A.K., Vrolijk, H., Tanke, H.J., Willemze, R., Landegent, J.E. Ann. Hematol. (1993) [Pubmed]
  18. Stimulation of human hematopoietic colony formation by recombinant gibbon multi-colony-stimulating factor or interleukin 3. Sieff, C.A., Niemeyer, C.M., Nathan, D.G., Ekern, S.C., Bieber, F.R., Yang, Y.C., Wong, G., Clark, S.C. J. Clin. Invest. (1987) [Pubmed]
  19. Interleukin-3 and interferon beta cooperate to induce differentiation of monocytes into dendritic cells with potent helper T-cell stimulatory properties. Buelens, C., Bartholomé, E.J., Amraoui, Z., Boutriaux, M., Salmon, I., Thielemans, K., Willems, F., Goldman, M. Blood (2002) [Pubmed]
  20. 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]
  21. Gene for the alpha-subunit of the human interleukin-3 receptor (IL3RA) localized to the X-Y pseudoautosomal region. Milatovich, A., Kitamura, T., Miyajima, A., Francke, U. Am. J. Hum. Genet. (1993) [Pubmed]
  22. Recombinant hematopoietic growth factors fail to induce a proliferative response in precursor B acute lymphoblastic leukemia. Touw, I., Groot-Loonen, J., Broeders, L., van Agthoven, T., Hählen, K., Hagemeijer, A., Löwenberg, B. Leukemia (1989) [Pubmed]
  23. Interleukin 2 infusion induces haemopoietic growth factors and modifies marrow regeneration after chemotherapy or autologous marrow transplantation. Heslop, H.E., Duncombe, A.S., Reittie, J.E., Bello-Fernandez, C., Gottlieb, D.J., Prentice, H.G., Mehta, A.B., Hoffbrand, A.V., Brenner, M.K. Br. J. Haematol. (1991) [Pubmed]
  24. Preservation of immature hematopoietic progenitor cells responding to interleukin 3 in marrow treated with 4-hydroperoxycyclophosphamide. Minegishi, N., Minegishi, M., Tuchiya, S., Konno, T. Tohoku J. Exp. Med. (1989) [Pubmed]
  25. Human peripheral blood basophils primed by interleukin 3 (IL-3) produce IL-4 in response to immunoglobulin E receptor stimulation. Brunner, T., Heusser, C.H., Dahinden, C.A. J. Exp. Med. (1993) [Pubmed]
  26. The receptor for interleukin 3 is selectively induced in human endothelial cells by tumor necrosis factor alpha and potentiates interleukin 8 secretion and neutrophil transmigration. Korpelainen, E.I., Gamble, J.R., Smith, W.B., Goodall, G.J., Qiyu, S., Woodcock, J.M., Dottore, M., Vadas, M.A., Lopez, A.F. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  27. IgE-independent interleukin-4 expression and induction of a late phase of leukotriene C4 formation in human blood basophils. Ochensberger, B., Rihs, S., Brunner, T., Dahinden, C.A. Blood (1995) [Pubmed]
  28. Steel factor induces serine phosphorylation of Stat3 in human growth factor-dependent myeloid cell lines. Gotoh, A., Takahira, H., Mantel, C., Litz-Jackson, S., Boswell, H.S., Broxmeyer, H.E. Blood (1996) [Pubmed]
  29. Human interleukin-3 (IL-3) induces disulfide-linked IL-3 receptor alpha- and beta-chain heterodimerization, which is required for receptor activation but not high-affinity binding. Stomski, F.C., Sun, Q., Bagley, C.J., Woodcock, J., Goodall, G., Andrews, R.K., Berndt, M.C., Lopez, A.F. Mol. Cell. Biol. (1996) [Pubmed]
  30. Human P40 T-cell growth factor (interleukin-9) supports erythroid colony formation. Donahue, R.E., Yang, Y.C., Clark, S.C. Blood (1990) [Pubmed]
  31. Structure of the activation domain of the GM-CSF/IL-3/IL-5 receptor common beta-chain bound to an antagonist. Rossjohn, J., McKinstry, W.J., Woodcock, J.M., McClure, B.J., Hercus, T.R., Parker, M.W., Lopez, A.F., Bagley, C.J. Blood (2000) [Pubmed]
  32. A model for assembly and activation of the GM-CSF, IL-3 and IL-5 receptors: insights from activated mutants of the common beta subunit. D'Andrea, R.J., Gonda, T.J. Exp. Hematol. (2000) [Pubmed]
  33. Interleukin-3/erythropoietin fusion proteins: in vitro effects on hematopoietic cells. Weich, N.S., Tullai, J., Guido, E., McMahon, M., Jolliffe, L.K., Lopez, A.F., Vadas, M.A., Lowry, P.A., Quesenberry, P.J., Rosen, J. Exp. Hematol. (1993) [Pubmed]
  34. Role of the adapter protein CRKL in signal transduction of normal hematopoietic and BCR/ABL-transformed cells. Sattler, M., Salgia, R. Leukemia (1998) [Pubmed]
  35. Role of tyrosine residues and protein interaction domains of SHC adaptor in VEGF receptor 3 signaling. Fournier, E., Blaikie, P., Rosnet, O., Margolis, B., Birnbaum, D., Borg, J.P. Oncogene (1999) [Pubmed]
  36. Growth and differentiation of the human megakaryoblastic cell line (ELF-153): a model for early stages of megakaryocytopoiesis. Mouthon, M.A., Freund, M., Titeux, M., Katz, A., Guichard, J., Breton-Gorius, J., Vainchenker, W. Blood (1994) [Pubmed]
  37. Stem cell factor influences the proliferation and erythroid differentiation of the MB-02 human erythroleukemia cell line by binding to a high-affinity c-kit receptor. Broudy, V.C., Morgan, D.A., Lin, N., Zsebo, K.M., Jacobsen, F.W., Papayannopoulou, T. Blood (1993) [Pubmed]
  38. Secretion of a unique peptide from interleukin-2-stimulated natural killer cells that induces endomitosis in immature human megakaryocytes. Angchaisuksiri, P., Grigus, S.R., Carlson, P.L., Krystal, G.W., Dessypris, E.N. Blood (2002) [Pubmed]
  39. Effects of recombinant human granulocyte colony-stimulating factor (CSF), human granulocyte macrophage-CSF, and gibbon interleukin-3 on hematopoiesis in human long-term bone marrow culture. Coutinho, L.H., Will, A., Radford, J., Schiró, R., Testa, N.G., Dexter, T.M. Blood (1990) [Pubmed]
  40. Regulation of interleukin-11 protein and mRNA expression in neonatal and adult fibroblasts and endothelial cells. Suen, Y., Chang, M., Lee, S.M., Buzby, J.S., Cairo, M.S. Blood (1994) [Pubmed]
  41. Effects of the stem cell factor, c-kit ligand, on human megakaryocytic cells. Avraham, H., Vannier, E., Cowley, S., Jiang, S.X., Chi, S., Dinarello, C.A., Zsebo, K.M., Groopman, J.E. Blood (1992) [Pubmed]
  42. Ex vivo expansion of enriched peripheral blood CD34+ progenitor cells by stem cell factor, interleukin-1 beta (IL-1 beta), IL-6, IL-3, interferon-gamma, and erythropoietin. Brugger, W., Möcklin, W., Heimfeld, S., Berenson, R.J., Mertelsmann, R., Kanz, L. Blood (1993) [Pubmed]
  43. Mast cell growth factor modulates CD36 antigen expression on erythroid progenitors from human bone marrow and peripheral blood associated with ongoing differentiation. de Wolf, J.T., Muller, E.W., Hendriks, D.H., Halie, R.M., Vellenga, E. Blood (1994) [Pubmed]
  44. A new hematopoietic cell line, KMT-2, having human interleukin-3 receptors. Tamura, S., Sugawara, M., Tanaka, H., Tezuka, E., Nihira, S., Miyamoto, C., Suda, T., Ohta, Y. Blood (1990) [Pubmed]
  45. Interleukin-4 has basophilic and eosinophilic cell growth-promoting activity on cord blood cells. Favre, C., Saeland, S., Caux, C., Duvert, V., De Vries, J.E. Blood (1990) [Pubmed]
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