Interleukin 18

IL18
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1J0S, 2VXT, 3F62, 4EEE, 4EKX, 4HJJ, 3WO2, 3WO3, 3WO4, 4R6U, 4XFS, 4XFT, 4XFU
Identifiers
Aliases	IL18, IGIF, IL-18, IL-1g, IL1F4, interleukin 18
External IDs	OMIM: 600953 MGI: 107936 HomoloGene: 1200 GeneCards: IL18
Gene location (Human)
Chr.	Chromosome 11 (human)[1]
End	112,164,117 bp[1]
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)[2]
End	50,581,840 bp[2]
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• protein binding; • cytokine activity; • interleukin-18 receptor binding;
Cellular component	• cytosol; • extracellular region; • extracellular space;
Biological process	• positive regulation of inflammatory response; • granulocyte macrophage colony-stimulating factor biosynthetic process; • cell-cell signaling; • cellular response to organic cyclic compound; • chemokine biosynthetic process; • type 2 immune response; • MAPK cascade; • positive regulation of natural killer cell proliferation; • sleep; • regulation of cell adhesion; • positive regulation of NK T cell proliferation; • positive regulation of granulocyte macrophage colony-stimulating factor production; • positive regulation of tissue remodeling; • angiogenesis; • T-helper 1 type immune response; • interleukin-13 biosynthetic process; • interleukin-2 biosynthetic process; • positive regulation of interleukin-17 production; • inflammatory response; • lipopolysaccharide-mediated signaling pathway; • positive regulation of activated T cell proliferation; • positive regulation of protein kinase B signaling; • positive regulation of phosphatidylinositol 3-kinase signaling; • positive regulation of smooth muscle cell proliferation; • activation of protein kinase B activity; • positive regulation of transcription from RNA polymerase II promoter; • positive regulation of tyrosine phosphorylation of STAT protein; • positive regulation of gene expression; • positive regulation of macrophage derived foam cell differentiation; • natural killer cell activation; • positive regulation of interferon-gamma production; • interferon-gamma biosynthetic process; • cholesterol homeostasis; • positive regulation of T-helper 2 cell differentiation; • negative regulation of myoblast differentiation; • triglyceride homeostasis; • cell proliferation; • regulation of receptor activity; • interferon-gamma production; • interleukin-6 production; • T-helper 1 cell cytokine production; • neutrophil activation; • natural killer cell mediated cytotoxicity; • cytokine-mediated signaling pathway; • interleukin-18-mediated signaling pathway; • positive regulation of NIK/NF-kappaB signaling; • immune response; • positive regulation of NF-kappaB transcription factor activity; • positive regulation of T-helper 1 cell cytokine production;
	Sources:Amigo / QuickGO
Orthologs
	3606
	16173
	ENSG00000150782
	ENSMUSG00000039217
	Q14116
	P70380
	NM_001243211; NM_001562
	NM_008360; NM_001357221; NM_001357222
	NP_001230140; NP_001553; NP_001230140.1
	NP_032386; NP_001344150; NP_001344151
	Wikidata
View/Edit Human	View/Edit Mouse

Interleukin-18 (IL18, also known as interferon-gamma inducing factor) is a protein which in humans is encoded by the IL18 gene.^[5]^[6] 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.^[7]

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.^[8]

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.^[9]

IL-18 has also been found to increase the Alzheimer's disease-associated amyloid-beta production in human neuron cells.^[10]

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000150782 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000039217 - Ensembl, May 2017
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ 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.
↑ 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.
↑ "Entrez Gene: IL18 interleukin 18 (interferon-gamma-inducing factor)".
↑ 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.
↑ 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.
↑ 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.

Interleukin 18

Function

Clinical significance

References

Further reading