WordNet

any of several lymphokines that promote macrophages and killer T cells and B cells and other components of the immune system

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/11 17:07:24」(JST)

wiki en

The interleukin 4 (IL4) 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 in a positive feedback loop. 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.

Function

It has many biological roles, including the stimulation of activated B-cell and T-cell proliferation, and the differentiation of B cells into plasma 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. 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]

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]

Receptor

The receptor for Interleukin-4 is known as the IL-4Rα. This receptor exists in 3 different complexes throughout the body. Type 1 receptors are composed of the IL-4Rα subunit with a common γ chain and specifically bind IL-4. Type 2 receptors consist of an IL-4Rα subunit bound to a different subunit known as IL-13Rα1. These type 2 receptors have the ability to bind both IL-4 and IL-13, two cytokines with closely related biological functions.^[4]^[5]

Structure

IL-4 has a compact, globular fold (similar to other cytokines), stabilised by 3 disulphide bonds.^[6] One half of the structure is dominated by a 4 alpha-helix bundle with a left-handed twist.^[7] The helices are anti-parallel, with 2 overhand connections, which fall into a 2-stranded anti-parallel beta-sheet.^[7]

Discovery

This cytokine was co-discovered by Maureen Howard and William Paul^[8] 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).^[9]

Clinical significance

IL-4 also has been shown to drive mitogenesis, dedifferentiation, and metastasis in rhabdomyosarcoma.^[10] IL-4, along with other Th2 cytokines, is involved in the airway inflammation observed in the lungs of patients with allergic asthma.

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.
^ Maes T, Joos GF, Brusselle GG (September 2012). "Targeting interleukin-4 in asthma: lost in translation?". Am. J. Respir. Cell Mol. Biol. 47 (3): 261–70. doi:10.1165/rcmb.2012-0080TR. PMID 22538865.
^ Chatila TA (October 2004). "Interleukin-4 receptor signaling pathways in asthma pathogenesis". Trends Mol Med 10 (10): 493–9. doi:10.1016/j.molmed.2004.08.004. PMID 15464449.
^ Carr C, Aykent S, Kimack NM, Levine AD (February 1991). "Disulfide assignments in recombinant mouse and human interleukin 4". Biochemistry 30 (6): 1515–23. doi:10.1021/bi00220a011. 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.
^ 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.

External links

Interleukin-4 at the US National Library of Medicine Medical Subject Headings (MeSH)
Interleukin-4 from Gentaur at Gentaur
Recombinant Human Interleukin-4 from Cornell University
Interleukin-4 from Allergy Glossary at Health On the Net Foundation

This article incorporates text from the public domain Pfam and InterPro IPR002354

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 肥満細胞由来のメディエーター mast cell derived mediators
2. ヘルパーT細胞サブセット：疾患における分化および役割 t helper subsets differentiation and role in disease
3. 喘息の病因 pathogenesis of asthma
4. 癌免疫療法の原則 principles of cancer immunotherapy
5. リウマチ性疾患におけるサイトカインネットワーク：治療の意味 cytokine networks in rheumatic diseases implications for therapy

English Journal

Platelet derived growth factor-CC secreted by M2 macrophages induces alpha-smooth muscle actin expression by dermal and gingival fibroblasts.

Glim JE, Niessen FB, Everts V, van Egmond M, Beelen RH.SourceDepartment of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands; Department of Plastic and Reconstructive Surgery, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: je.glim@vumc.nl.
Immunobiology.Immunobiology.2013 Jun;218(6):924-9. doi: 10.1016/j.imbio.2012.10.004. Epub 2012 Oct 26.
Dermal wounds can heal detrimentally by formation of excess fibrosis or hypertrophic scarring. These phenomena are normally absent in the oral mucosa. Macrophages play an important role in wound repair, have a marked heterogeneity and are thought to contribute to fibrosis. To investigate to what ext
PMID 23182716

Interleukin-4-induced loss of CD8 expression and cytolytic function in effector CD8 T cells persists long term in vivo.

Olver S, Apte SH, Baz A, Kelso A, Kienzle N.SourceThe Cooperative Research Centre for Vaccine Technology and the Queensland Institute of Medical Research, Herston, Qld, Australia.
Immunology.Immunology.2013 Jun;139(2):187-96. doi: 10.1111/imm.12068.
Activation of naive CD8(+) T cells in the presence of interleukin-4 modulates their CD8 co-receptor expression and functional differentiation, resulting in the generation of CD8(low) cells that produce type 2 cytokines and display poor cytolytic and anti-tumour activity. Although this CD8(low) pheno
PMID 23311920

Japanese Journal

A distinct human CD4+ T cell subset that secretes CXCL13 in rheumatoid synovitis.

Kobayashi Shio,Murata Koichi,Shibuya Hideyuki,Morita Mami,Ishikawa Masahiro,Furu Moritoshi,Ito Hiromu,Ito Juichi,Matsuda Shuichi,Watanabe Takeshi,Yoshitomi Hiroyuki
Arthritis and rheumatism, 2013-09-10
… 2013-09-20.[Objective] ]Human CD4+ T cells in synovitis of rheumatoid arthritis (RA) produce CXCL13, a chemokine crucial for the formation of germinal center. … [Methods] The expression of Th markers and CXCL13 in CD4+ T cells of RA synovitis and the involvement of proinflammatory cytokines in CXCL13 production were assessed. … We also investigated whether CXCL13+CD4+ T cells could be newly induced. …
NAID 120005327027

Mast Cell Stabilizing Effect of (-)‐Elema‐1,3,11(13)‐trien‐12‐ol and Thujopsene from Thujopsis dolabrata Is Mediated by Down‐Regulation of Interleukin‐4 Secretion in Antigen‐Induced RBL‐2H3 Cells

Kim Chul-Hee,Lee Taehun,Oh Ikhoon [他]
Biological & pharmaceutical bulletin 36(3), 339-345, 2013-03-00
NAID 40019588153

Effect of Eriodictyol on the Development of Atopic Dermatitis-Like Lesions in ICR Mice

Park Sae-Jin,Lee Yong-Hyeon,Lee Kwang Ho,Kim Tack-Joong
Biological and Pharmaceutical Bulletin 36(8), 1375-1379, 2013
… Our previous studies have reported that eriodictyol extract inhibits immunoglobulin E (IgE)/Ag-induced type I hypersensitivity by suppressing the activation of proinflammatory cytokines, such as interleukin-4 (IL-4), and the expression of ceramide kinase. … In this study, we investigated the inhibitory effect of eriodictyol on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in ICR mice. …
NAID 130003361497

Related Pictures

★リンクテーブル★

リンク元	「IL-4」
拡張検索	「interleukin-4 receptor」「type II interleukin-4 receptor」「type I interleukin-4 receptor」「interleukin-4 receptor alpha subunit」
関連記事	「interleukin」「interleukins」

「IL-4」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Interleukin 4
	analysis of the solution structure of human interleukin 4 determined by heteronuclear three-dimensional nuclear magnetic resonance techniques
Identifiers
Symbol	IL4
Pfam	PF00727
Pfam clan	CL0053
InterPro	IPR002354
PROSITE	PDOC00655
SCOP	2int
SUPERFAMILY	2int
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Interleukin 4
	Crystal structure of human IL-4 (2INT)
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1BBN, 1BCN, 1CYL, 1HIJ, 1HIK, 1HZI, 1IAR, 1ILL, 1ITE, 1ITI, 1ITL, 1ITM, 1RCB, 2B8U, 2B8X, 2B8Y, 2B8Z, 2B90, 2B91, 2CYK, 2D48, 2INT, 3BPL, 3BPN, 3QB7, 4YDY
Identifiers
Symbols	IL4 ; BCGF-1; BCGF1; BSF-1; BSF1; IL-4
External IDs	OMIM: 147780 MGI: 96556 HomoloGene: 491 GeneCards: IL4 Gene
Gene ontology
Molecular function	• cytokine activity; • interleukin-4 receptor binding; • protein binding; • growth factor activity;
Cellular component	• extracellular space; • external side of plasma membrane;
Biological process	• microglial cell activation; • innate immune response in mucosa; • positive regulation of defense response to virus by host; • T-helper 1 cell lineage commitment; • negative regulation of acute inflammatory response; • negative regulation of chronic inflammatory response; • chemotaxis; • immune response; • cellular defense response; • female pregnancy; • response to nutrient; • cholesterol metabolic process; • regulation of proton transport; • negative regulation of epithelial cell migration; • response to organic cyclic compound; • B cell differentiation; • positive regulation of B cell proliferation; • B cell costimulation; • positive regulation of interleukin-10 production; • positive regulation of interleukin-13 production; • response to cytokine; • T-helper 2 cell cytokine production; • type 2 immune response; • positive regulation of T cell proliferation; • positive regulation of activated T cell proliferation; • regulation of phosphorylation; • response to drug; • positive regulation of tyrosine phosphorylation of Stat5 protein; • defense response to protozoan; • negative regulation of macrophage activation; • negative regulation of apoptotic process; • positive regulation of mast cell degranulation; • negative regulation of nitric oxide biosynthetic process; • T-helper 2 cell differentiation; • positive regulation of chemokine biosynthetic process; • connective tissue growth factor biosynthetic process; • regulation of isotype switching; • positive regulation of MHC class II biosynthetic process; • response to ethanol; • positive regulation of T cell differentiation; • negative regulation of osteoclast differentiation; • negative regulation of transcription, DNA-templated; • positive regulation of transcription, DNA-templated; • positive regulation of transcription from RNA polymerase II promoter; • positive regulation of isotype switching to IgE isotypes; • positive regulation of isotype switching to IgG isotypes; • regulation of immune response; • positive regulation of sequence-specific DNA binding transcription factor activity; • retina development in camera-type eye; • negative regulation of white fat cell proliferation; • cellular response to mercury ion; • positive regulation of mononuclear cell migration; • dendritic cell differentiation; • extrinsic apoptotic signaling pathway in absence of ligand; • positive regulation of myoblast fusion; • negative regulation of complement-dependent cytotoxicity; • negative regulation of T-helper 17 cell differentiation; • negative regulation of endothelial cell apoptotic process; • positive regulation of eosinophil chemotaxis; • negative regulation of extrinsic apoptotic signaling pathway;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;