Interleukin 18

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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


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