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Interleukin 3 (IL-3) is a protein that in humans is encoded by the IL3 gene localised on chromosome 15q31.1[3][4].

IL3
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesIL3, interleukin 3, IL-3, MCGF, MULTI-CSF
External IDsOMIM: 147740 HomoloGene: 47938 GeneCards: IL3
Gene location (Human)
Chromosome 5 (human)
Chr.Chromosome 5 (human)[1]
Chromosome 5 (human)
Genomic location for IL3
Genomic location for IL3
Band5q31.1Start132,060,529 bp[1]
End132,063,204 bp[1]
RNA expression pattern
PBB GE IL3 207906 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000588

n/a

RefSeq (protein)

NP_000579

n/a

Location (UCSC)Chr 5: 132.06 – 132.06 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Synonyms: colony-stimulating factor; mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399.

The protein contains 152 amino acids and its molecular weight is 17 kDa.

IL-3 is produced as a monomer by activated T cells, monocytes/macrophages and stroma cells. [5]

Contents

ImportanceEdit

The major function of IL-3 cytokine is to regulate blood-cell production [6][7]. It induces proliferation and differentiation of early pluripotent stem cells and committed progenitors [8].

FunctionEdit

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.

ReceptorEdit

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 surface interleukin-3 receptor and IL-3.[9] 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) [10]. This β subunit sharing explains the biological functional similarities of different hematopoietic growth factors [11].

IL-3/Receptor complex induces JAK2/STAT5 cell signalisation pathway. It can stimulate transcription factor c‑myc (activation of gene expression) and Ras pathway (suppression of apoptosis) [12].

DiscoveryEdit

Interleukin 3 was originally 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.[13][14]

In the early 1960s Ginsberg and Sachs discovered that IL-3 is a potent mast cell growth factor produced from activated T cells [9].

DiseaseEdit

IL-3 is produced by T cells only after stimulation with antigens or other specific impulses.

However, it was observed that IL-3 is constitutively present in the myelomonocytic leukaemia cell line WEHI-3B. It is thought that this genetic change is the key in development of this leukaemia type [15]

Immunological therapyEdit

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 of granulocytes and platelets. However, only IL-3 treatment in bone marrow failure disorders such as myelodysplastic syndrome (MDS) and aplastic anemia (AA) was disappointing. [11]

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].

InteractionsEdit

Interleukin 3 has been shown to interact with IL3RA.[20][21]

See alsoEdit

ReferencesEdit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000164399 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:".
  3. ^ "Entrez Gene: IL3 interleukin 3 (colony-stimulating factor, multiple)".
  4. ^ 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. PMID 3489530.
  5. ^ "IL3 (interleukin-3)". atlasgeneticsoncology.org. Retrieved 2019-06-19.
  6. ^ Aiguo, Wu; Guangren, Duan (July 2006). "PMID Observer Design of Descriptor Linear Systems". 2007 Chinese Control Conference. IEEE: 161–165. doi:10.1109/chicc.2006.4347343. ISBN 9787811240559.
  7. ^ Aiguo, Wu; Guangren, Duan (July 2006). "PMID Observer Design of Descriptor Linear Systems". 2007 Chinese Control Conference. IEEE: 161–165. doi:10.1109/chicc.2006.4347343. ISBN 9787811240559.
  8. ^ 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. ISSN 1066-5099. PMID 8401260.
  9. ^ a b Delves, Peter J.; Roitt, Ivan Maurice, eds. (1998). Encyclopedia of immunology (2nd ed.). San Diego: Academic Press. ISBN 0122267656. OCLC 36017792.
  10. ^ 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. ISSN 0340-6717. PMID 8112746.
  11. ^ a b Manzoor H Mangi, Adrian C Newland. "Interleukin-3 in hematology and onkology: Current state of knowledge and future directions". Cytokines, Cellular and Molecular Therapy. 5: 87–95.
  12. ^ "IL3 (interleukin-3)". atlasgeneticsoncology.org. Retrieved 2019-06-19.
  13. ^ 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. PMID 6971890.
  14. ^ Ihle JN, Weinstein Y, Keller J, Henderson L, Palaszynski E (1985). Interleukin 3. Meth. Enzymol. Methods in Enzymology. 116. pp. 540–52. doi:10.1016/S0076-6879(85)16042-8. ISBN 978-0-12-182016-9. PMID 3003517.
  15. ^ Aiguo, Wu; Guangren, Duan (July 2006). "PMID Observer Design of Descriptor Linear Systems". 2007 Chinese Control Conference. IEEE: 161–165. doi:10.1109/chicc.2006.4347343. ISBN 9787811240559.
  16. ^ 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. PMID 3087441.
  17. ^ 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. PMID 7711665.
  18. ^ 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. PMID 8547656.
  19. ^ Hirst, WJR; 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. ISSN 0969-7128. PMID 9282170.
  20. ^ 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. PMC 231298. PMID 8649415.
  21. ^ 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. PMC 395466. PMID 7957082.

Further readingEdit