Interleukin 4
| Interleukin 4 |
Crystal structure of human IL-4 (2INT) |
| Available structures |
| PDB |
1BBN, 1BCN, 1CYL, 1HIJ, 1HIK, 1HZI, 1IAR, 1ILL, 1ITE, 1ITI, 1ITL, 1ITM, 1RCB, 2B8U, 2B8X, 2B8Y, 2B8Z, 2B90, 2B91, 2CYK, 2D48, 2INT, 3BPL, 3BPN |
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| Identifiers |
| Symbols |
IL4; BCGF-1; BCGF1; BSF-1; BSF1; IL-4; MGC79402 |
| External IDs |
OMIM: 147780 MGI: 96556 HomoloGene: 491 GeneCards: IL4 Gene |
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| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
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| Entrez |
3565 |
16189 |
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| Ensembl |
ENSG00000113520 |
ENSMUSG00000000869 |
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| UniProt |
P05112 |
Q5SV00 |
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| RefSeq (mRNA) |
NM_000589.2 |
NM_021283 |
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| RefSeq (protein) |
NP_000580.1 |
NP_067258.1 |
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| Location (UCSC) |
Chr 5:
132.01 – 132.02 Mb |
Chr 11:
53.42 – 53.43 Mb |
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| PubMed search |
[1] |
[2] |
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Interleukin-4, abbreviated IL-4, is a cytokine that induces differentiation of naive helper T cells (Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4. The cell that initially produces IL-4, thus inducing Th0 differentiation, has not been identified, but recent studies suggest that basophils may be the effector cell.[1] It is closely related and has functions similar to Interleukin 13.
Its receptor is the Interleukin-4 receptor.
Functions
It has many biological roles, including the stimulation of activated B-cell and T-cell proliferation, and the differentiation of CD4+ T-cells into Th2 cells.
It is a key regulator in humoral and adaptive immunity.
IL-4 induces B-cell class switching to IgE, and up-regulates MHC class II production. It also induces B cell class switching to IgG4.
IL-4 decreases the production of Th1 cells, macrophages, IFN-gamma, and dendritic cell IL-12.
Overproduction of IL-4 is associated with allergies.[2]
In inflammation and wound repair
Tissue macrophages play an important role in chronic inflammation and wound repair. The presence of IL-4 in extravascular tissues promotes alternative activation of macrophages into M2 cells and inhibits classical activation of macrophages into M1 cells. An increase in repair macrophages (M2) is coupled with secretion of IL-10 and TGF-β that result in a diminution of pathological inflammation. Release of arginase, proline, polyaminases and TGF-β by the activated M2 cell is tied with wound repair and fibrosis.[3]
Clinical significance
IL-4 also has been shown to drive mitogenesis, dedifferentiation, and metastasis in rhabdomyosarcoma.[4]
Structure
IL-4 has a compact, globular fold (similar to other cytokines), stabilised by 3 disulphide bonds.[5] One half of the structure is dominated by a 4 alpha-helix bundle with a left-handed twist.[6] The helices are anti-parallel, with 2 overhand connections, which fall into a 2-stranded anti-parallel beta-sheet.[6]
History
This cytokine was co-discovered by Maureen Howard and William Paul[7] and by Dr. Ellen Vitetta and her research group in 1982.
The nucleotide sequence for human IL-4 was isolated four years later confirming its similarity to a mouse protein called B-cell stimulatory factor-1 (BCSF-1).[8]
See also
References
- ^ Sokol, C.L., Barton, G.M., Farr, A.G. & Medzhitov, R. (2008). "A mechanism for the initiation of allergen-induced T helper type 2 responses". Nat Immunol 9 (3): 310–318. doi:10.1038/ni1558. PMID 18300366.
- ^ Hershey GK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA (December 1997). "The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor". N. Engl. J. Med. 337 (24): 1720–5. doi:10.1056/NEJM199712113372403. PMID 9392697. Lay summary – eurekalert.org.
- ^ Jon Aster, Vinay Kumar, Abul K. Abbas; Nelson Fausto (2009). Robbins & Cotran Pathologic Basis of Disease (8th ed.). Philadelphia: Saunders. p. 54. ISBN 1-4160-3121-9.
- ^ Hosoyama T, Aslam MI, Abraham J, Prajapati SI, Nishijo K, Michalek JE, Zarzabal LA, Nelon LD, Guttridge DC, Rubin BP, Keller C (May 2011). "IL-4R Drives Dedifferentiation, Mitogenesis, and Metastasis in Rhabdomyosarcoma". Clin Cancer Res 17 (9): 2757–2766. doi:10.1158/1078-0432.CCR-10-3445. PMC 3087179. PMID 21536546. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3087179.
- ^ Carr C, Aykent S, Kimack NM, Levine AD (February 1991). "Disulfide assignments in recombinant mouse and human interleukin 4". Biochemistry 30 (6): 1515-23. PMID 1993171.
- ^ a b Walter MR, Cook WJ, Zhao BG, Cameron RP, Ealick SE, Walter RL, Reichert P, Nagabhushan TL, Trotta PP, Bugg CE (October 1992). "Crystal structure of recombinant human interleukin-4". J. Biol. Chem. 267 (28): 20371-6. PMID 1400355.
- ^ Howard M, Paul WE (1982). "Interleukins for B lymphocytes". Lymphokine Res. 1 (1): 1–4. PMID 6985399.
- ^ Yokota T et al. (1986). "Isolation and characterization of a human interleukin cDNA clone, homologous to mouse B-cell stimulatory factor 1, that expresses B-cell- and T-cell-stimulating activities". Proc. Natl. Acad. Sci. U.S.A. 83 (16): 5894–8. doi:10.1073/pnas.83.16.5894. PMC 386403. PMID 3016727. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=386403.
Further reading
- Apte SH, Baz A, Kelso A, Kienzle N (2008). "Interferon-gamma and interleukin-4 reciprocally regulate CD8 expression in CD8+ T cells". Proc Natl Acad Sci U S A. 105 (45): 17475–80. doi:10.1073/pnas.0809549105. PMC 2580749. PMID 18988742. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2580749.
- Kay AB, Barata L, Meng Q, et al. (1997). "Eosinophils and eosinophil-associated cytokines in allergic inflammation". Int. Arch. Allergy Immunol. 113 (1–3): 196–9. doi:10.1159/000237545. PMID 9130521.
- Marone G, Florio G, Petraroli A, de Paulis A (2001). "Dysregulation of the IgE/Fc epsilon RI network in HIV-1 infection". J. Allergy Clin. Immunol. 107 (1): 22–30. doi:10.1067/mai.2001.111589. PMID 11149986.
- Marone G, Florio G, Triggiani M, et al. (2001). "Mechanisms of IgE elevation in HIV-1 infection". Crit. Rev. Immunol. 20 (6): 477–96. PMID 11396683.
- Maeda S, Yanagihara Y (2001). "[Inflammatory cytokines (IL-4, IL-5 and IL-13)]". Nippon Rinsho 59 (10): 1894–9. PMID 11676128.
- Izuhara K, Arima K, Yasunaga S (2003). "IL-4 and IL-13: their pathological roles in allergic diseases and their potential in developing new therapies". Current drug targets. Inflammation and allergy 1 (3): 263–9. doi:10.2174/1568010023344661. PMID 14561191.
- Copeland KF (2006). "Modulation of HIV-1 transcription by cytokines and chemokines". Mini reviews in medicinal chemistry 5 (12): 1093–101. doi:10.2174/138955705774933383. PMID 16375755.
- Olver S, Apte S, Baz A, Kienzle N (2007). "The duplicitous effects of interleukin 4 on tumour immunity: how can the same cytokine improve or impair control of tumour growth?". Tissue Antigens 69 (4): 293–8. doi:10.1111/j.1399-0039.2007.00831.x. PMID 17389011.
- Sokol CL, Chu NQ, Shuang Yu, Simone Nish, Terri Laufer & Ruslan Medzhitov (2009). "Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response". Nature Immunology 10 (7): 713–720. doi:10.1038/ni.1738. PMID 19465907.
- Sokol CL, Chu NQ, Yu S, Nish SA, Laufer TM, Medzhitov R (July 2009). "Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response". Nat. Immunol. 10 (7): 713–20. doi:10.1038/ni.1738. PMID 19465907.
External links
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PDB gallery
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1bbn: THREE-DIMENSIONAL SOLUTION STRUCTURE OF HUMAN INTERLEUKIN-4 BY MULTI-DIMENSIONAL HETERONUCLEAR MAGNETIC RESONANCE SPECTROSCOPY
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1bcn: THREE-DIMENSIONAL SOLUTION STRUCTURE OF HUMAN INTERLEUKIN-4 BY MULTI-DIMENSIONAL HETERONUCLEAR MAGNETIC RESONANCE SPECTROSCOPY
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1cyl: ASPECTS OF RECEPTOR BINDING AND SIGNALLING OF INTERLEUKIN-4 INVESTIGATED BY SITE-DIRECTED MUTAGENESIS AND NMR SPECTROSCOPY
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1hij: INTERLEUKIN-4 MUTANT WITH ARG 88 REPLACED WITH GLN (R88Q)
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1hik: INTERLEUKIN-4 (WILD-TYPE)
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1hzi: INTERLEUKIN-4 MUTANT E9A
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1iar: INTERLEUKIN-4 / RECEPTOR ALPHA CHAIN COMPLEX
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1iti: THE HIGH RESOLUTION THREE-DIMENSIONAL SOLUTION STRUCTURE OF HUMAN INTERLEUKIN-4 DETERMINED BY MULTI-DIMENSIONAL HETERONUCLEAR MAGNETIC RESONANCE SPECTROSCOPY
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1itl: HUMAN INTERLEUKIN 4: THE SOLUTION STRUCTURE OF A FOUR-HELIX-BUNDLE PROTEIN
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1itm: ANALYSIS OF THE SOLUTION STRUCTURE OF HUMAN INTERLEUKIN 4 DETERMINED BY HETERONUCLEAR THREE-DIMENSIONAL NUCLEAR MAGNETIC RESONANCE TECHNIQUES
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1rcb: CRYSTAL STRUCTURE OF HUMAN RECOMBINANT INTERLEUKIN-4 AT 2.25 ANGSTROMS RESOLUTION
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2b8u: Crystal structure of wildtype human Interleukin-4
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2b8x: Crystal stucture of the interleukin-4 variant F82D
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2b8y: Crystal structure of the interleukin-4 variant T13DF82D
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2b8z: Crystal structure of the interleukin-4 variant R85A
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2b90: Crystal structure of the interleukin-4 variant T13DR85A
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2b91: Crystal structure of the interleukin-4 variant F82DR85A
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2cyk: ASPECTS OF RECEPTOR BINDING AND SIGNALLING OF INTERLEUKIN-4 INVESTIGATED BY SITE-DIRECTED MUTAGENESIS AND NMR SPECTROSCOPY
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2d48: Crystal structure of the Interleukin-4 variant T13D
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2int: CRYSTAL STRUCTURE OF RECOMBINANT HUMAN INTERLEUKIN-4
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Type I
(grouped by
receptor
subunit)
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IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21, IFNB1, IFNK, IFNW1
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Other
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By function/
cell |
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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This article incorporates text from the public domain Pfam and InterPro IPR002354