Interleukin 3
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Interleukin 3 (IL-3) is a protein that in humans is encoded by the IL3 gene localized 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-3 cytokine is to regulate the concentrations of various blood-cell types.[6] It induces proliferation and differentiation in both early pluripotent stem cells and committed progenitors.[7][8] It also has many more specific effects like the regeneration of platelets and potentially aids in early antibody isotype switching.[9][10]
Function
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.[10] In conjunction with other β common chain cytokines GM-CSF and IL-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 the interleukin-3 receptor.[9][10]
IL-3 is mainly produced by activated
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 of platelets via the development of megakaryocytes.[10]
Interleukin 3 stimulates the differentiation of
IL-3 is secreted by basophils and activated
Receptor
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.[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 immature myelomonocytic cells in the hemopoietic system such as hemopoietic progenitor cells, as well as certain myeloid progenitors, basophils, and eosinophils.[10]
IL-3/Receptor complex induces JAK2/STAT5 cell signalization pathway.[8] It can stimulate transcription factor c‑myc (activation of gene expression) and Ras pathway (suppression of apoptosis).[5]
Discovery
In the early 1960s Ginsberg and Sachs discovered that IL-3 is a potent mast cell growth factor produced from activated T 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
IL-3 is produced by T cells only after stimulation with antigens or 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
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.[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
Interleukin 3 has been shown to
See also
References
- ^ a b c GRCh38: 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)".
- S2CID 37207637.
- ^ a b "IL3 (interleukin-3)". atlasgeneticsoncology.org. Archived from the original on 2022-02-05. Retrieved 2019-06-19.
- ^ S2CID 72187.
- S2CID 27772987.
- ^ PMID 9766809.
- ^ PMID 32976908.
- ^ PMID 30995500.
- ^ OCLC 36017792.
- S2CID 34492340.
- ^ PMID 10515681.
- S2CID 20592584.
- PMID 3003517.
- PMID 3087441.
- PMID 7711665.
- PMID 8547656.
- PMID 9282170.
- PMID 8649415.
- PMID 7957082.
Further reading
- Wagemaker G, Burger H, van Gils FC, van Leen RW, Wielenga JJ (1990). "Interleukin-3". Biotherapy. 2 (4): 337–45. S2CID 195122011.
- 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. PMID 14564341.
- Mroczko B, Szmitkowski M (2004). "Hematopoietic cytokines as tumor markers". Clin. Chem. Lab. Med. 42 (12): 1347–54. S2CID 11414705.
- 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. S2CID 42948973.
- 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. S2CID 35647863.
- 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. S2CID 10373990.
- 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. S2CID 37207637.
- 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. PMID 3497400.
- 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. PMID 3497843.
- 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. PMID 7642615.
- 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. PMID 8018916.
- 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. PMID 8516290.
- 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. PMID 8649415.
- 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. PMID 8676386.
- Vanhaesebroeck B, PMID 9113989.
- 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. PMID 9278420.
- 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. S2CID 25068171.
- 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. S2CID 30047980.
- 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. PMID 9659156.