Interleukin 3 is an interleukin, a type of biological signal (cytokine) that can improve the body's natural response to disease as part of the immune system. It acts by binding to the interleukin-3 receptor.
Interleukin 3 stimulates the differentiation of multipotent hematopoietic stem cells into myeloid progenitor cells or, with the addition of IL-7, into lymphoid progenitor cells. In addition, IL-3 stimulates proliferation of all cells in the myeloid lineage (granulocytes, monocytes, and dendritic cells), in conjunction with other cytokines, e.g., Erythropoietin (EPO), Granulocyte macrophage colony-stimulating factor (GM-CSF), and IL-6. It is secreted by basophils and activated T cells to support growth and differentiation of T cells from the bone marrow in an immune response. Activated T cells can either induce their own proliferation and differentiation (autocrine signalling), or that of other T cells (paracrine signalling) – both involve IL-2 binding to the IL-2 receptor on T cells (upregulated upon cell activation, under the induction of macrophage-secreted IL-1). The human IL-3 gene encodes a protein 152 amino acids long, and the naturally occurring IL-3 is glycosylated. The human IL-3 gene is located on chromosome 5, only 9 kilobases from the GM-CSF gene, and its function is quite similar to GM-CSF.
Discovery
Interleukin 3 originally was discovered by JN Ihle in mice. He found a T cell derived factor that induced the synthesis of 20alpha-hydroxysteroid dehydrogenase in hematopoietic cells and termed it interleukin-3.[3][4]
Wagemaker G, Burger H, van Gils FC, van Leen RW, Wielenga JJ (1990). "Interleukin-3". Biotherapy. 2 (4): 337–45. doi:10.1007/BF02170083. PMID2268499.
Martinez-Moczygemba M, Huston DP (2003). "Biology of common beta receptor-signaling cytokines: IL-3, IL-5, and GM-CSF". J. Allergy Clin. Immunol. 112 (4): 653–65, quiz 666. doi:10.1016/j.jaci.2003.08.015. PMID14564341.
Mroczko B, Szmitkowski M (2004). "Hematopoietic cytokines as tumor markers". Clin. Chem. Lab. Med. 42 (12): 1347–54. doi:10.1515/CCLM.2004.253. PMID15576295.
Kitamura T, Sato N, Arai K, Miyajima A (1991). "Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors". Cell. 66 (6): 1165–74. doi:10.1016/0092-8674(91)90039-2. PMID1833064.
Urdal DL, Price V, Sassenfeld HM, Cosman D, Gillis S, Park LS (1989). "Molecular characterization of colony-stimulating factors and their receptors: human interleukin-3". Ann. N. Y. Acad. Sci. 554: 167–76. doi:10.1111/j.1749-6632.1989.tb22418.x. PMID2544122.
Otsuka T, Miyajima A, Brown N, Otsu K, Abrams J, Saeland S, Caux C, de Waal Malefijt R, de Vries J, Meyerson P (1988). "Isolation and characterization of an expressible cDNA encoding human IL-3. Induction of IL-3 mRNA in human T cell clones". J. Immunol. 140 (7): 2288–95. PMID3127463.
Yang YC, Ciarletta AB, Temple PA, Chung MP, Kovacic S, Witek-Giannotti JS, Leary AC, Kriz R, Donahue RE, Wong GG (1986). "Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3". Cell. 47 (1): 3–10. doi:10.1016/0092-8674(86)90360-0. PMID3489530.
Dorssers L, Burger H, Bot F, Delwel R, Geurts van Kessel AH, Löwenberg B, Wagemaker G (1987). "Characterization of a human multilineage-colony-stimulating factor cDNA clone identified by a conserved noncoding sequence in mouse interleukin-3". Gene. 55 (1): 115–24. doi:10.1016/0378-1119(87)90254-X. PMID3497843.
Chirmule N, Goonewardena H, Pahwa S, Pasieka R, Kalyanaraman VS, Pahwa S (1995). "HIV-1 envelope glycoproteins induce activation of activated protein-1 in CD4+ T cells". J. Biol. Chem. 270 (33): 19364–9. doi:10.1074/jbc.270.33.19364. PMID7642615.
Than S, Oyaizu N, Pahwa RN, Kalyanaraman VS, Pahwa S (1994). "Effect of human immunodeficiency virus type-1 envelope glycoprotein gp160 on cytokine production from cord-blood T cells". Blood. 84 (1): 184–8. PMID8018916.
Feng Y, Klein BK, McWherter CA (1996). "Three-dimensional solution structure and backbone dynamics of a variant of human interleukin-3". J. Mol. Biol. 259 (3): 524–41. doi:10.1006/jmbi.1996.0337. PMID8676386.
Klein BK, Feng Y, McWherter CA, Hood WF, Paik K, McKearn JP (1997). "The receptor binding site of human interleukin-3 defined by mutagenesis and molecular modeling". J. Biol. Chem. 272 (36): 22630–41. doi:10.1074/jbc.272.36.22630. PMID9278420.
Sanchez X, Suetomi K, Cousins-Hodges B, Horton JK, Navarro J (1998). "CXC chemokines suppress proliferation of myeloid progenitor cells by activation of the CXC chemokine receptor 2". J. Immunol. 160 (2): 906–10. PMID9551928.
Tabira T, Chui DH, Fan JP, Shirabe T, Konishi Y (1998). "Interleukin-3 and interleukin-3 receptors in the brain". Ann. N. Y. Acad. Sci. 840: 107–16. doi:10.1111/j.1749-6632.1998.tb09554.x. PMID9629242.