Interleukin 18: Difference between revisions

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{{ otheruses4|a cytokine|the Soviet aircraft|Ilyushin Il-18 }}
{{for|the Soviet four-engined turboprop airliner dubbed "Il-18"|Ilyushin Il-18}}
{{PBB_Controls
{{Infobox_gene}}
| update_page = yes
'''Interleukin-18''' ('''IL18''', also known as '''interferon-gamma inducing factor''') is a [[protein]] which in humans is encoded by the ''IL18'' [[gene]].<ref name="pmid7477296">{{cite journal |vauthors=Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K | title = Cloning of a new cytokine that induces IFN-gamma production by T cells | journal = Nature | volume = 378 | issue = 6552 | pages = 88–91 |date=November 1995 | pmid = 7477296 | doi = 10.1038/378088a0 | url = }}</ref><ref name="pmid9693051">{{cite journal |vauthors=Nolan KF, Greaves DR, Waldmann H | title = The human interleukin 18 gene IL18 maps to 11q22.2-q22.3, closely linked to the DRD2 gene locus and distinct from mapped IDDM loci | journal = Genomics | volume = 51 | issue = 1 | pages = 161–3 |date=July 1998 | pmid = 9693051 | doi = 10.1006/geno.1998.5336 | url =  }}</ref> The protein encoded by this gene is a [[proinflammatory cytokine]].
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| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}
<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image = IL18_Solution_Structure.rsh.png
| image_source = Solution structure of human IL-18
| PDB = {{PDB2|1j0s}}
| Name = Interleukin 18 (interferon-gamma-inducing factor)
| HGNCid = 5986
| Symbol = IL18
| AltSymbols =; IGIF; IL-18; IL-1g; IL1F4; MGC12320
| OMIM = 600953
| ECnumber = 
| Homologene = 1200
| MGIid = 107936
| GeneAtlas_image1 = PBB_GE_IL18_206295_at_tn.png
| Function = {{GNF_GO|id=GO:0004871 |text = signal transducer activity}} {{GNF_GO|id=GO:0005149 |text = interleukin-1 receptor binding}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}}
| Process = {{GNF_GO|id=GO:0001525 |text = angiogenesis}} {{GNF_GO|id=GO:0006955 |text = immune response}} {{GNF_GO|id=GO:0007267 |text = cell-cell signaling}} {{GNF_GO|id=GO:0008625 |text = induction of apoptosis via death domain receptors}} {{GNF_GO|id=GO:0030155 |text = regulation of cell adhesion}} {{GNF_GO|id=GO:0030431 |text = sleep}} {{GNF_GO|id=GO:0042033 |text = chemokine biosynthetic process}} {{GNF_GO|id=GO:0042088 |text = T-helper 1 type immune response}} {{GNF_GO|id=GO:0042092 |text = T-helper 2 type immune response}} {{GNF_GO|id=GO:0042094 |text = interleukin-2 biosynthetic process}} {{GNF_GO|id=GO:0042095 |text = interferon-gamma biosynthetic process}} {{GNF_GO|id=GO:0042104 |text = positive regulation of activated T cell proliferation}} {{GNF_GO|id=GO:0042231 |text = interleukin-13 biosynthetic process}} {{GNF_GO|id=GO:0042253 |text = granulocyte macrophage colony-stimulating factor biosynthetic process}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3606
    | Hs_Ensembl = ENSG00000150782
    | Hs_RefseqProtein = NP_001553
    | Hs_RefseqmRNA = NM_001562
    | Hs_GenLoc_db =   
    | Hs_GenLoc_chr = 11
    | Hs_GenLoc_start = 111519186
    | Hs_GenLoc_end = 111540050
    | Hs_Uniprot = Q14116
    | Mm_EntrezGene = 16173
    | Mm_Ensembl = ENSMUSG00000039217
    | Mm_RefseqmRNA = NM_008360
    | Mm_RefseqProtein = NP_032386
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 9
    | Mm_GenLoc_start = 50327503
    | Mm_GenLoc_end = 50334067
    | Mm_Uniprot = A0PJ18
  }}
}}


'''Interleukin-18''' (IL-18) is a [[cytokine]] produced by [[macrophage]]s and other cells that belongs to the [[IL-1]] superfamily.  IL-18 works together with [[IL-12]] to induce [[cell-mediated immunity]] following infection with microbial products like [[lipopolysaccharide]] (LPS).  After stimulation with IL-18, [[natural killer cells|natural killer]] (NK) cells and certain [[T cells]] release another important cytokine called interferon-γ (IFN-γ) or type II interferon that plays an important role in activating the macrophages or other cells. Apart from its physiological role, IL-18 is also able to induce severe [[inflammation|inflammatory reactions]], which suggests its role in certain inflammatory disorders.
== Function ==
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =  
| summary_text = The protein encoded by this gene is a proinflammatory cytokine. This cytokine can induce the IFN-gamma production of T cells. The combination of this cytokine and IL12 has been shown to inhibit IL4 dependent IgE and IgG1 production, and enhance IgG2a production of B cells. IL-18 binding protein (IL18BP) can specifically interact with this cytokine, and thus negatively regulate its biological activity.<ref>{{cite web | title = Entrez Gene: IL18 interleukin 18 (interferon-gamma-inducing factor)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3606| accessdate = }}</ref>
}}


==References==
IL-18 is a [[cytokine]] that belongs to the [[Interleukin 1|IL-1]] superfamily and is produced by [[macrophage]]s and other cells. IL-18 works by binding to the [[interleukin-18 receptor]], and together with [[Interleukin 12|IL-12]] it induces [[cell-mediated immunity]] following infection with microbial products like [[lipopolysaccharide]] (LPS).  After stimulation with IL-18, [[natural killer cells|natural killer]] (NK) cells and certain [[T cells]] release another important cytokine called [[interferon-gamma|interferon-γ]] (IFN-γ) or type II interferon that plays an important role in activating the macrophages or other cells.
{{reflist|2}}
 
==Further reading==
The combination of this cytokine and IL12 has been shown to inhibit [[interleukin 4|IL-4]] dependent [[immunoglobulin E|IgE]] and [[immunoglobulin G|IgG1]] production, and enhance IgG2a production in [[B cell]]s. IL-18 binding protein ([[IL18BP]]) can specifically interact with this cytokine, and thus negatively regulate its biological activity.<ref>{{cite web | title = Entrez Gene: IL18 interleukin 18 (interferon-gamma-inducing factor)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3606| accessdate = }}</ref>
{{refbegin | 2}}
 
{{PBB_Further_reading
== Clinical significance ==
| citations =
 
*{{cite journal  | author=Biet F, Locht C, Kremer L |title=Immunoregulatory functions of interleukin 18 and its role in defense against bacterial pathogens. |journal=J. Mol. Med. |volume=80 |issue= 3 |pages= 147-62 |year= 2002 |pmid= 11894141 |doi= 10.1007/s00109-001-0307-1 }}
Apart from its physiological role, IL-18 is also able to induce severe [[inflammation|inflammatory reactions]], which suggests its role in certain inflammatory disorders.
*{{cite journal  | author=Nakanishi K |title=[Regulation of Th1 and Th2 immune responses by IL-18] |journal=Kekkaku |volume=77 |issue= 2 |pages= 87-93 |year= 2002 |pmid= 11905033 |doi=  }}
 
*{{cite journal  | author=Reddy P, Ferrara JL |title=Role of interleukin-18 in acute graft-vs-host disease. |journal=J. Lab. Clin. Med. |volume=141 |issue= 6 |pages= 365-71 |year= 2003 |pmid= 12819633 |doi= 10.1016/S0022-2143(03)00028-3 }}
Endometrial [[IL-18 receptor]] mRNA and the ratio of [[IL18BP|IL-18 binding protein]] to interleukin 18 are significantly increased in [[adenomyosis]] patients in comparison to normal people, indicating a role in its pathogenesis.<ref name="pmid19394601">{{cite journal |vauthors=Huang HY, Yu HT, Chan SH, Lee CL, Wang HS, Soong YK | title = Eutopic endometrial interleukin-18 system mRNA and protein expression at the level of endometrial-myometrial interface in adenomyosis patients | journal = Fertil. Steril. | volume = 94 | issue = 1 | pages = 33–9 |date=June 2010 | pmid = 19394601 | doi = 10.1016/j.fertnstert.2009.01.132 | url =  }}</ref>
*{{cite journal | author=Kanai T, Uraushihara K, Totsuka T, ''et al.'' |title=Macrophage-derived IL-18 targeting for the treatment of Crohn's disease. |journal=Current drug targets. Inflammation and allergy |volume=2 |issue= 2 |pages= 131-6 |year= 2003 |pmid= 14561165 |doi=  }}
 
*{{cite journal  | author=Matsui K, Tsutsui H, Nakanishi K |title=Pathophysiological roles for IL-18 in inflammatory arthritis. |journal=Expert Opin. Ther. Targets |volume=7 |issue= 6 |pages= 701-24 |year= 2005 |pmid= 14640907 |doi= 10.1517/14728222.7.6.701 }}
IL-18 has been implicated as an inflammatory mediator of [[Hashimoto's thyroiditis]], the most common  cause of autoimmune hypothyroidism.  IL-18 is up regulated by [[interferon-gamma]].<ref name="pmid20586818">{{cite journal |vauthors=Liu Z, Wang H, Xiao W, Wang C, Liu G, Hong T | title = Thyrocyte interleukin-18 expression is up-regulated by interferon-γ and may contribute to thyroid destruction in Hashimoto's thyroiditis | journal = Int J Exp Pathol | volume = 91 | issue = 5 | pages = 420–5 |date=October 2010 | pmid = 20586818 | doi = 10.1111/j.1365-2613.2010.00715.x | url = | pmc = 3003839 }}</ref>
*{{cite journal  | author=Yoshimoto T, Nakanishi K |title=Roles of IL-18 in basophils and mast cells. |journal=Allergology international : official journal of the Japanese Society of Allergology |volume=55 |issue= 2 |pages= 105-13 |year= 2006 |pmid= 17075246 |doi= 10.2332/allergolint.55.105 }}
 
*{{cite journal  | author=Orozco A, Gemmell E, Bickel M, Seymour GJ |title=Interleukin 18 and periodontal disease. |journal=J. Dent. Res. |volume=86 |issue= 7 |pages= 586-93 |year= 2007 |pmid= 17586702 |doi=  }}
IL-18 has also been found to increase the [[Alzheimer's]] disease-associated [[amyloid-beta]] production in human neuron cells.<ref name="pmid22898493">{{cite journal |vauthors=Sutinen EM, Pirttilä T, Anderson G, Salminen A, Ojala JO | title = Pro-inflammatory interleukin-18 increases Alzheimer's disease-associated amyloid-β production in human neuron-like cells | journal = J Neuroinflammation | volume = 9 | issue = | pages = 199 | year = 2012 | pmid = 22898493 | pmc = 3458954 | doi = 10.1186/1742-2094-9-199 }}</ref>
}}
 
== References ==
{{reflist}}
 
== Further reading ==
{{Refbegin|2}}
*{{cite journal  |vauthors=Biet F, Locht C, Kremer L |title=Immunoregulatory functions of interleukin 18 and its role in defense against bacterial pathogens |journal=J. Mol. Med. |volume=80 |issue= 3 |pages= 147–62 |year= 2002 |pmid= 11894141 |doi= 10.1007/s00109-001-0307-1 }}
*{{cite journal  | author=Nakanishi K |title=[Regulation of Th1 and Th2 immune responses by IL-18] |journal=Kekkaku |volume=77 |issue= 2 |pages= 87–93 |year= 2002 |pmid= 11905033 |doi=  }}
*{{cite journal  |vauthors=Reddy P, Ferrara JL |title=Role of interleukin-18 in acute graft-vs-host disease |journal=J. Lab. Clin. Med. |volume=141 |issue= 6 |pages= 365–71 |year= 2003 |pmid= 12819633 |doi= 10.1016/S0022-2143(03)00028-3 }}
*{{cite journal   |vauthors=Kanai T, Uraushihara K, Totsuka T, etal |title=Macrophage-derived IL-18 targeting for the treatment of Crohn's disease |journal=Current drug targets. Inflammation and allergy |volume=2 |issue= 2 |pages= 131–6 |year= 2003 |pmid= 14561165 |doi=10.2174/1568010033484250 }}
*{{cite journal  |vauthors=Matsui K, Tsutsui H, Nakanishi K |title=Pathophysiological roles for IL-18 in inflammatory arthritis |journal=Expert Opin. Ther. Targets |volume=7 |issue= 6 |pages= 701–24 |year= 2005 |pmid= 14640907 |doi= 10.1517/14728222.7.6.701 }}
*{{cite journal  |vauthors=Yoshimoto T, Nakanishi K |title=Roles of IL-18 in basophils and mast cells |journal=Allergology International  |volume=55 |issue= 2 |pages= 105–13 |year= 2006 |pmid= 17075246 |doi= 10.2332/allergolint.55.105 }}
*{{cite journal  |vauthors=Orozco A, Gemmell E, Bickel M, Seymour GJ |title=Interleukin 18 and periodontal disease |journal=J. Dent. Res. |volume=86 |issue= 7 |pages= 586–93 |year= 2007 |pmid= 17586702 |doi=10.1177/154405910708600702 }}
{{refend}}
{{refend}}


{{immunology-stub}}
{{PDB Gallery|geneid=3606}}
{{interleukins}}
{{Interleukins}}
{{Interleukin receptor modulators}}


[[pl:Interleukina 18]]
[[Category:Interleukins]]
{{WikiDoc Sources}}

Latest revision as of 00:18, 27 October 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
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View/Edit Human

Interleukin-18 (IL18, also known as interferon-gamma inducing factor) is a protein which in humans is encoded by the IL18 gene.[1][2] The protein encoded by this gene is a proinflammatory cytokine.

Function

IL-18 is a cytokine that belongs to the IL-1 superfamily and is produced by macrophages and other cells. IL-18 works by binding to the interleukin-18 receptor, and together with IL-12 it induces cell-mediated immunity following infection with microbial products like lipopolysaccharide (LPS). After stimulation with IL-18, natural killer (NK) cells and certain T cells release another important cytokine called interferon-γ (IFN-γ) or type II interferon that plays an important role in activating the macrophages or other cells.

The combination of this cytokine and IL12 has been shown to inhibit IL-4 dependent IgE and IgG1 production, and enhance IgG2a production in B cells. IL-18 binding protein (IL18BP) can specifically interact with this cytokine, and thus negatively regulate its biological activity.[3]

Clinical significance

Apart from its physiological role, IL-18 is also able to induce severe inflammatory reactions, which suggests its role in certain inflammatory disorders.

Endometrial IL-18 receptor mRNA and the ratio of IL-18 binding protein to interleukin 18 are significantly increased in adenomyosis patients in comparison to normal people, indicating a role in its pathogenesis.[4]

IL-18 has been implicated as an inflammatory mediator of Hashimoto's thyroiditis, the most common cause of autoimmune hypothyroidism. IL-18 is up regulated by interferon-gamma.[5]

IL-18 has also been found to increase the Alzheimer's disease-associated amyloid-beta production in human neuron cells.[6]

References

  1. Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K (November 1995). "Cloning of a new cytokine that induces IFN-gamma production by T cells". Nature. 378 (6552): 88–91. doi:10.1038/378088a0. PMID 7477296.
  2. Nolan KF, Greaves DR, Waldmann H (July 1998). "The human interleukin 18 gene IL18 maps to 11q22.2-q22.3, closely linked to the DRD2 gene locus and distinct from mapped IDDM loci". Genomics. 51 (1): 161–3. doi:10.1006/geno.1998.5336. PMID 9693051.
  3. "Entrez Gene: IL18 interleukin 18 (interferon-gamma-inducing factor)".
  4. Huang HY, Yu HT, Chan SH, Lee CL, Wang HS, Soong YK (June 2010). "Eutopic endometrial interleukin-18 system mRNA and protein expression at the level of endometrial-myometrial interface in adenomyosis patients". Fertil. Steril. 94 (1): 33–9. doi:10.1016/j.fertnstert.2009.01.132. PMID 19394601.
  5. Liu Z, Wang H, Xiao W, Wang C, Liu G, Hong T (October 2010). "Thyrocyte interleukin-18 expression is up-regulated by interferon-γ and may contribute to thyroid destruction in Hashimoto's thyroiditis". Int J Exp Pathol. 91 (5): 420–5. doi:10.1111/j.1365-2613.2010.00715.x. PMC 3003839. PMID 20586818.
  6. Sutinen EM, Pirttilä T, Anderson G, Salminen A, Ojala JO (2012). "Pro-inflammatory interleukin-18 increases Alzheimer's disease-associated amyloid-β production in human neuron-like cells". J Neuroinflammation. 9: 199. doi:10.1186/1742-2094-9-199. PMC 3458954. PMID 22898493.

Further reading