Interleukin 10 Information & Interleukin 10 Links at HealthHaven.com

Interleukin 10
	PDB rendering based on 2H24.
Available structures
	1ilk, 1inr, 1j7v, 1lk3, 1vlk, 1y6k, 1y6m, 1y6n, 2h24, 2ilk
Identifiers
Symbols	IL10; CSIF; IL-10; IL10A; MGC126450; MGC126451; TGIF
External IDs	OMIM: 124092 MGI: 96537 HomoloGene: 478
Gene ontology
Molecular function	• cytokine activity; • interleukin-10 receptor binding; • protein binding;
Cellular component	• extracellular region; • extracellular space;
Biological process	• anti-apoptosis; • inflammatory response; • immune response; • cytoplasmic sequestering of NF-kappaB; • cell-cell signaling; • hemopoiesis; • B cell differentiation; • leukocyte chemotaxis; • T-helper 2 type immune response; • B cell proliferation; • negative regulation of T cell proliferation; • defense response to bacterium; • negative regulation of nitric oxide biosynthetic process; • negative regulation of interferon-gamma biosynthetic process; • regulation of isotype switching; • negative regulation of MHC class II biosynthetic process; • positive regulation of MHC class II biosynthetic process; • negative regulation of interferon-alpha biosynthetic process;
RNA expression pattern
	More reference expression data
Orthologs
NP_000563 (protein)	NP_034678 (protein)

edit

Interleukin-10 (IL-10 or IL10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine. In humans IL-10 is encoded by the IL10 gene.^[1]

This cytokine is produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II antigens, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-κB activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract.^[2] and indeed patients with Crohn's disease react favorably towards treatment with bacteria producing recombinant interleukin 10, showing the importance of interleukin 10 for counteracting excessive immunity in the human body.^[3]

A study in mice has shown that interleukin-10 is also produced by mast cells, counteracting the inflammatory effect that these cells have at the site of an allergic reaction.^[4]

[edit] Function

It is capable of inhibiting synthesis of pro-inflammatory cytokines like IFN-γ, IL-2, IL-3, TNFα and GM-CSF made by cells such as macrophages and the Type 1 T helper cells.

IL-10 also displays potent abilities to suppress the antigen presentation capacity of antigen presenting cells.

However, it is also stimulatory towards certain T cells, mast cells and stimulates B cell maturation and antibody production.

[edit] Expression

It is mainly expressed in monocytes and Type 2 T helper cells (T_H2), mast cells, CD4+CD25+Foxp3+ regulatory T cells, and also in a certain subset of activated T cells and B cells.

It is released by cytotoxic T-cells to inhibit the actions of NK cells during the immune response to viral infection.

[edit] Gene and protein structure

In humans, the IL-10 gene is located in chromosome 1 and consists of 5 exons.^[1]

The IL-10 protein is a homodimer . Each subunit is 178 amino acids long.^[5]

[edit] Interactions

Interleukin 10 has been shown to interact with Interleukin 10 receptor, alpha subunit.^[6]^[7]^[8]^[9]^[10]

[edit] References

^ ^a ^b Eskdale J, Kube D, Tesch H, Gallagher G (1997). "Mapping of the human IL10 gene and further characterization of the 5' flanking sequence". Immunogenetics 46 (2): 120–8. PMID 9162098.
^ "Entrez Gene: IL10 interleukin 10". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3586.
^ Braat H, Rottiers P, Hommes DW, Huyghebaert N, Remaut E, Remon JP, van Deventer SJ, Neirynck S, Peppelenbosch MP, Steidler L (June 2006). "A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease". Clin. Gastroenterol. Hepatol. 4 (6): 754–9. doi:10.1016/j.cgh.2006.03.028. PMID 16716759.
^ Grimbaldeston MA, Nakae S, Kalesnikoff J, Tsai M, Galli SJ (October 2007). "Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B". Nat. Immunol. 8 (10): 1095–104. doi:10.1038/ni1503. PMID 17767162.
^ Zdanov A, Schalk-Hihi C, Gustchina A, Tsang M, Weatherbee J, Wlodawer A (June 1995). "Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma". Structure 3 (6): 591–601. PMID 8590020.
^ Ho, A S; Liu Y, Khan T A, Hsu D H, Bazan J F, Moore K W (Dec. 1993). "A receptor for interleukin 10 is related to interferon receptors". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 90 (23): 11267-71. ISSN 0027-8424. PMID 8248239.
^ Josephson, K; Logsdon N J, Walter M R (Jul. 2001). "Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site". Immunity (United States) 15 (1): 35-46. ISSN 1074-7613. PMID 11485736.
^ Tan, J C; Braun S, Rong H, DiGiacomo R, Dolphin E, Baldwin S, Narula S K, Zavodny P J, Chou C C (May. 1995). "Characterization of recombinant extracellular domain of human interleukin-10 receptor". J. Biol. Chem. (UNITED STATES) 270 (21): 12906-11. ISSN 0021-9258. PMID 7759550.
^ Josephson, K; McPherson D T, Walter M R (Dec. 2001). "Purification, crystallization and preliminary X-ray diffraction of a complex between IL-10 and soluble IL-10R1". Acta Crystallogr. D Biol. Crystallogr. (Denmark) 57 (Pt 12): 1908-11. ISSN 0907-4449. PMID 11717514.
^ Hoover, D M; Schalk-Hihi C, Chou C C, Menon S, Wlodawer A, Zdanov A (May. 1999). "Purification of receptor complexes of interleukin-10 stoichiometry and the importance of deglycosylation in their crystallization". Eur. J. Biochem. (GERMANY) 262 (1): 134-41. ISSN 0014-2956. PMID 10231374.

[edit] Further reading

Bortesi L, Rossato M, Schuster F, Raven N, Stadlmann J, Avesani L, Falorni A, Bazzoni F, Bock R, Schillberg S, Pezzotti M (2009). "Viral and murine interleukin-10 are correctly processed and retain their biological activity when produced in tobacco". BMC Biotechnol. 9: 22. doi:10.1186/1472-6750-9-22. PMID 19298643.
Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A (2001). "Interleukin-10 and the interleukin-10 receptor". Annu. Rev. Immunol. 19: 683–765. doi:10.1146/annurev.immunol.19.1.683. PMID 11244051.
Girndt M (2003). "Humoral immune responses in uremia and the role of IL-10". Blood Purif. 20 (5): 485–8. doi:10.1159/000063553. PMID 12207099.
Beebe AM, Cua DJ, de Waal Malefyt R (2003). "The role of interleukin-10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS)". Cytokine Growth Factor Rev. 13 (4-5): 403–12. doi:10.1016/S1359-6101(02)00025-4. PMID 12220553.
Mocellin S, Panelli MC, Wang E, et al. (2004). "The dual role of IL-10". Trends Immunol. 24 (1): 36–43. doi:10.1016/S1471-4906(02)00009-1. PMID 12495723.
Roncarolo MG, Battaglia M, Gregori S (2004). "The role of interleukin 10 in the control of autoimmunity". J. Autoimmun. 20 (4): 269–72. doi:10.1016/S0896-8411(03)00047-7. PMID 12791310.
Groux H, Cottrez F (2004). "The complex role of interleukin-10 in autoimmunity". J. Autoimmun. 20 (4): 281–5. doi:10.1016/S0896-8411(03)00044-1. PMID 12791313.
Llorente L, Richaud-Patin Y (2004). "The role of interleukin-10 in systemic lupus erythematosus". J. Autoimmun. 20 (4): 287–9. doi:10.1016/S0896-8411(03)00043-X. PMID 12791314.
Asadullah K, Sabat R, Friedrich M, et al. (2004). "Interleukin-10: an important immunoregulatory cytokine with major impact on psoriasis". Current drug targets. Inflammation and allergy 3 (2): 185–92. doi:10.2174/1568010043343886. PMID 15180472.
Stenvinkel P, Ketteler M, Johnson RJ, et al. (2005). "IL-10, IL-6, and TNF-alpha: central factors in the altered cytokine network of uremia--the good, the bad, and the ugly". Kidney Int. 67 (4): 1216–33. doi:10.1111/j.1523-1755.2005.00200.x. PMID 15780075.
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.

[edit] External links

MeSH Interleukin-10

This immunology article is a stub. You can help Wikipedia by expanding it.

[pmid9162098-0] Eskdale J, Kube D, Tesch H, Gallagher G (1997). "Mapping of the human IL10 gene and further characterization of the 5' flanking sequence". Immunogenetics 46 (2): 120–8. PMID 9162098.

[1] "Entrez Gene: IL10 interleukin 10". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3586.

[pmid16716759-2] Braat H, Rottiers P, Hommes DW, Huyghebaert N, Remaut E, Remon JP, van Deventer SJ, Neirynck S, Peppelenbosch MP, Steidler L (June 2006). "A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease". Clin. Gastroenterol. Hepatol. 4 (6): 754–9. doi:10.1016/j.cgh.2006.03.028. PMID 16716759.

[pmid17767162-3] Grimbaldeston MA, Nakae S, Kalesnikoff J, Tsai M, Galli SJ (October 2007). "Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B". Nat. Immunol. 8 (10): 1095–104. doi:10.1038/ni1503. PMID 17767162.

[pmid8590020-4] Zdanov A, Schalk-Hihi C, Gustchina A, Tsang M, Weatherbee J, Wlodawer A (June 1995). "Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma". Structure 3 (6): 591–601. PMID 8590020.

[pmid8248239-5] Ho, A S; Liu Y, Khan T A, Hsu D H, Bazan J F, Moore K W (Dec. 1993). "A receptor for interleukin 10 is related to interferon receptors". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 90 (23): 11267-71. ISSN 0027-8424. PMID 8248239.

[pmid11485736-6] Josephson, K; Logsdon N J, Walter M R (Jul. 2001). "Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site". Immunity (United States) 15 (1): 35-46. ISSN 1074-7613. PMID 11485736.

[pmid7759550-7] Tan, J C; Braun S, Rong H, DiGiacomo R, Dolphin E, Baldwin S, Narula S K, Zavodny P J, Chou C C (May. 1995). "Characterization of recombinant extracellular domain of human interleukin-10 receptor". J. Biol. Chem. (UNITED STATES) 270 (21): 12906-11. ISSN 0021-9258. PMID 7759550.

[pmid11717514-8] Josephson, K; McPherson D T, Walter M R (Dec. 2001). "Purification, crystallization and preliminary X-ray diffraction of a complex between IL-10 and soluble IL-10R1". Acta Crystallogr. D Biol. Crystallogr. (Denmark) 57 (Pt 12): 1908-11. ISSN 0907-4449. PMID 11717514.

[pmid10231374-9] Hoover, D M; Schalk-Hihi C, Chou C C, Menon S, Wlodawer A, Zdanov A (May. 1999). "Purification of receptor complexes of interleukin-10 stoichiometry and the importance of deglycosylation in their crystallization". Eur. J. Biochem. (GERMANY) 262 (1): 134-41. ISSN 0014-2956. PMID 10231374.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

Contents