Interleukin 3
Interleukin 3(IL-3) is aproteinthat inhumansis encoded by theIL3genelocalized on chromosome 5q31.1.[3][4]Sometimes also called colony-stimulating factor, multi-CSF, mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399: after removal of the signal peptide sequence, the mature protein contains 133 amino acids in its polypeptide chain. IL-3 is produced as a monomer by activated T cells, monocytes/macrophages and stroma cells.[5]The major function of IL-3cytokineis to regulate the concentrations of various blood-cell types.[6]It induces proliferation and differentiation in both early pluripotentstem cellsand committedprogenitors.[7][8]It also has many more specific effects like the regeneration ofplateletsand potentially aids in early antibodyisotype switching.[9][10]
Function[edit]
Interleukin 3 is aninterleukin,a type of biological signal (cytokine) that can improve the body's natural response to disease as part of theimmune system.[10]In conjunction with other β common chain cytokinesGM-CSFandIL-5,IL-3 works to regulate the inflammatory response in order to clear pathogens by changing the abundance of various cell populations via binding at theinterleukin-3 receptor.[9][10]
IL-3 is mainly produced by activatedT cellswith the goal of initiating proliferation of various other immune cell types.[8]However, IL-3 has also been shown to be produced inIgG+B cellsand may be involved in earlier antibodyisotype switching.[9]IL-3 is capable of stimulating differentiation of immaturemyelomonocytic cellscausing changes to themacrophageandgranulocytepopulations.[8]IL-3 signaling is able to give rise to widest array of cell lineages which is why it has been independently named “multi-CSF” in some older literature.[10]
IL-3 also induces various effector functions in both immature and mature cells that more precisely modulate the body’s defense against microbial pathogens.[8][10]IL-3 is also involved in the reconstruction ofplateletsvia the development ofmegakaryocytes.[10]
Interleukin 3 stimulates the differentiation ofmultipotent hematopoietic stem cellsintomyeloid progenitor cellsor, with the addition of IL-7, intolymphoid progenitor cells.In addition, IL-3 stimulates proliferation of all cells in the myeloid lineage (granulocytes,monocytes,anddendritic cells), in conjunction with other cytokines, e.g.,Erythropoietin(EPO),Granulocyte macrophage colony-stimulating factor(GM-CSF), andIL-6.
IL-3 is secreted by basophils and activatedT cellsto support growth and differentiation ofT cellsfrom the bone marrow in an immune response. ActivatedT cellscan either induce their own proliferation and differentiation (autocrinesignaling), or that of otherT cells(paracrinesignaling) – both involveIL-2binding to theIL-2 receptoronT cells(upregulated upon cell activation, under the induction ofmacrophage-secretedIL-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 onchromosome 5,only 9 kilobases from theGM-CSFgene, and its function is quite similar to GM-CSF.
Receptor[edit]
IL-3 is a T cell-derived, pluripotent and hematopoietic factor required for survival and proliferation of hematopoietic progenitor cells. The signal transmission is ensured by high affinity between cell surfaceinterleukin-3 receptorand IL-3.[11]This high affinity receptor contains α and β subunits. IL-3 shares the β subunit with IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF).[12]This β subunit sharing explains the biological functional similarities of different hematopoietic growth factors.[13]
IL-3 receptors can be found on a variety of cell types including many immaturemyelomonocytic cellsin thehemopoietic systemsuch as hemopoietic progenitor cells, as well as certain myeloid progenitors,basophils,andeosinophils.[10]
IL-3/Receptor complex inducesJAK2/STAT5cell signalization pathway.[8]It can stimulate transcription factorc‑myc(activation of gene expression) andRas pathway(suppression of apoptosis).[5]
Discovery[edit]
In the early 1960s Ginsberg and Sachs discovered that IL-3 is a potent mast cell growth factor produced from activatedT cells.[11]Interleukin 3 was originally discovered in mice and later isolated from humans. The cytokine was originally discovered via the observation that it induced the synthesis of 20alpha-hydroxysteroid dehydrogenase in hematopoietic cells and termed it interleukin-3 (IL-3).[14][15]
Disease[edit]
IL-3 is produced by T cells only after stimulation withantigensor other specific impulses.
However, it was observed that IL-3 is present in the myelomonocytic leukaemia cell line WEHI-3B. It is thought that this genetic change is the key in development of this leukemia type.[6]
Immunological therapy[edit]
Human IL-3 was first cloned in 1986 and since then clinical trials are ongoing.[16]Post-chemotherapy, IL-3 application reduces chemotherapy delays and promotes regeneration ofgranulocytesandplatelets.However, only IL-3 treatment in bone marrow failure disorders such asmyelodysplastic syndrome(MDS) andaplastic anemia(AA) was disappointing.[13]
It has been shown that combination of IL-3, GM-CSF and stem cell factor enhances peripheral blood stem cells during high-dose chemotherapy.[17][18]
Other studies showed that IL-3 could be a future perspective therapeutic agent in lymphohematopoietic disorders and solid cancers.[19]
Interactions[edit]
Interleukin 3 has been shown tointeractwithIL3RA.[20][21]
See also[edit]
References[edit]
- ^abcGRCh38: Ensembl release 89: ENSG00000164399–Ensembl,May 2017
- ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^"Entrez Gene: IL3 interleukin 3 (colony-stimulating factor, multiple)".
- ^Yang YC, Ciarletta AB, Temple PA, Chung MP, Kovacic S, Witek-Giannotti JS, Leary AC, Kriz R, Donahue RE, Wong GG (October 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.S2CID37207637.
- ^ab"IL3 (interleukin-3)".atlasgeneticsoncology.org.Archived fromthe originalon 2022-02-05.Retrieved2019-06-19.
- ^abAiguo W, Guangren D (July 2006). "PMID Observer Design of Descriptor Linear Systems".2007 Chinese Control Conference.IEEE. pp. 161–165.doi:10.1109/chicc.2006.4347343.ISBN978-7-81124-055-9.S2CID72187.
- ^Aglietta M, Pasquino P, Sanavio F, Stacchini A, Severino A, Fubini L, Morelli S, Volta C, Monteverde A (1996-01-01). "Granulocyte-Macrophage colony stimulating factor and interleukin 3: Target cells and kinetics of response in vivo".Stem Cells.11(S2): 83–87.doi:10.1002/stem.5530110814.ISSN1066-5099.PMID8401260.S2CID27772987.
- ^abcdeGuthridge MA, Stomski FC, Thomas D, Woodcock JM, Bagley CJ, Berndt MC, Lopez AF (September 1998)."Mechanism of Activation of the GM-CSF, IL-3, and IL-5 Family of Receptors".Stem Cells.16(5): 301–313.doi:10.1002/stem.160301.ISSN1066-5099.PMID9766809.
- ^abcWang AA, Gommerman JL, Rojas OL (January 2021)."Plasma Cells: From Cytokine Production to Regulation in Experimental Autoimmune Encephalomyelitis".Journal of Molecular Biology.433(1): 166655.doi:10.1016/j.jmb.2020.09.014.ISSN0022-2836.PMID32976908.
- ^abcdefgDougan M, Dranoff G, Dougan SK (April 2019)."GM-CSF, IL-3, and IL-5 Family of Cytokines: Regulators of Inflammation".Immunity.50(4): 796–811.doi:10.1016/j.immuni.2019.03.022.ISSN1074-7613.PMID30995500.
- ^abDelves, Peter J., Roitt, Ivan Maurice, eds. (1998).Encyclopedia of immunology(2nd ed.). San Diego: Academic Press.ISBN0-12-226765-6.OCLC36017792.
- ^Takai S, Yamada K, Hirayama N, Miyajima A, Taniyama T (February 1994). "Mapping of the human gene encoding the mutual signal-transducing subunit (?-chain) of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5) receptor complexes to chromosome 22q13.1".Human Genetics.93(2): 198–200.doi:10.1007/bf00210610.ISSN0340-6717.PMID8112746.S2CID34492340.
- ^abManzoor H Mangi AC (1999). "Interleukin-3 in hematology and onkology: Current state of knowledge and future directions".Cytokines, Cellular and Molecular Therapy.5(2): 87–95.PMID10515681.
- ^Ihle JN, Pepersack L, Rebar L (June 1981)."Regulation of T cell differentiation: in vitro induction of 20 alpha-hydroxysteroid dehydrogenase in splenic lymphocytes from athymic mice by a unique lymphokine".J. Immunol.126(6): 2184–9.doi:10.4049/jimmunol.126.6.2184.PMID6971890.S2CID20592584.
- ^Ihle JN, Weinstein Y, Keller J, Henderson L, Palaszynski E (1985). "Interleukin 3".Immunochemical Techniques Part H.Methods in Enzymology. Vol. 116. pp. 540–52.doi:10.1016/S0076-6879(85)16042-8.ISBN978-0-12-182016-9.PMID3003517.
- ^Metcalf D, Begley CG, Johnson GR, et al. (1986)."Effects of purified bacterially synthesised murine multi CSF (IL3) on hematopoiesis in normal adult mice".Blood.68(1): 46–57.doi:10.1182/blood.V68.1.46.46.PMID3087441.
- ^Serrano F, Varas F, Bernard A, Bueren JA (1994). "Accelerated and longterm hematopoietic engraftment in mice transplanted with ex-vivo expanded bone marrow".Bone Marrow Transplant.14(6): 855–62.PMID7711665.
- ^Peters SO, Kittler EL, Ramshaw HS, Quesenberry PJ (1996)."Ex-vivo expansion of murine marrow cells with IL-3, Il-6, Il-11 and SCF leads to impaired engraftment in irradiated host".Blood.87(1): 30–7.doi:10.1182/blood.V87.1.30.30.PMID8547656.
- ^Hirst W, Buggins A, Darling D, Gäken J, Farzaneh F, Mufti GJ (July 1997)."Enhanced immune costimulatory activity of primary acute myeloid leukaemia blasts after retrovirus-mediated gene transfer of B7.1".Gene Therapy.4(7): 691–699.doi:10.1038/sj.gt.3300437.ISSN0969-7128.PMID9282170.
- ^Stomski FC, Sun Q, Bagley CJ, Woodcock J, Goodall G, Andrews RK, Berndt MC, Lopez AF (June 1996)."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".Mol. Cell. Biol.16(6): 3035–46.doi:10.1128/MCB.16.6.3035.PMC231298.PMID8649415.
- ^Woodcock JM, Zacharakis B, Plaetinck G, Bagley CJ, Qiyu S, Hercus TR, Tavernier J, Lopez AF (November 1994)."Three residues in the common beta chain of the human GM-CSF, IL-3 and IL-5 receptors are essential for GM-CSF and IL-5 but not IL-3 high affinity binding and interact with Glu21 of GM-CSF".EMBO J.13(21): 5176–85.doi:10.1002/j.1460-2075.1994.tb06848.x.PMC395466.PMID7957082.
Further reading[edit]
- 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.S2CID195122011.
- 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.S2CID11414705.
- 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.S2CID42948973.
- 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(1): 167–76.Bibcode:1989NYASA.554..167U.doi:10.1111/j.1749-6632.1989.tb22418.x.PMID2544122.S2CID35647863.
- 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.doi:10.4049/jimmunol.140.7.2288.PMID3127463.S2CID10373990.
- 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.S2CID37207637.
- Le Beau MM, Epstein ND, O'Brien SJ, Nienhuis AW, Yang YC, Clark SC, Rowley JD (1987)."The interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q".Proc. Natl. Acad. Sci. U.S.A.84(16): 5913–7.Bibcode:1987PNAS...84.5913L.doi:10.1073/pnas.84.16.5913.PMC298973.PMID3497400.
- 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.doi:10.1182/blood.V84.1.184.184.PMID8018916.
- Le Beau MM, Espinosa R, Neuman WL, Stock W, Roulston D, Larson RA, Keinanen M, Westbrook CA (1993)."Cytogenetic and molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases".Proc. Natl. Acad. Sci. U.S.A.90(12): 5484–8.Bibcode:1993PNAS...90.5484B.doi:10.1073/pnas.90.12.5484.PMC46745.PMID8516290.
- Stomski FC, Sun Q, Bagley CJ, Woodcock J, Goodall G, Andrews RK, Berndt MC, Lopez AF (1996)."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".Mol. Cell. Biol.16(6): 3035–46.doi:10.1128/MCB.16.6.3035.PMC231298.PMID8649415.
- 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.CiteSeerX10.1.1.521.3736.doi:10.1006/jmbi.1996.0337.PMID8676386.
- Vanhaesebroeck B,Welham MJ,Kotani K, Stein R, Warne PH, Zvelebil MJ, Higashi K, Volinia S, Downward J, Waterfield MD (1997)."P110delta, a novel phosphoinositide 3-kinase in leukocytes".Proc. Natl. Acad. Sci. U.S.A.94(9): 4330–5.Bibcode:1997PNAS...94.4330V.doi:10.1073/pnas.94.9.4330.PMC20722.PMID9113989.
- 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.doi:10.4049/jimmunol.160.2.906.PMID9551928.S2CID25068171.
- 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(1): 107–16.Bibcode:1998NYASA.840..107T.doi:10.1111/j.1749-6632.1998.tb09554.x.PMID9629242.S2CID30047980.
- Nilsen EM, Johansen FE, Jahnsen FL, Lundin KE, Scholz T, Brandtzaeg P, Haraldsen G (1998)."Cytokine profiles of cultured microvascular endothelial cells from the human intestine".Gut.42(5): 635–42.doi:10.1136/gut.42.5.635.PMC1727090.PMID9659156.
