Interleukin 18
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Interleukin-18
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| Location (UCSC) | Chr 11: 112.14 – 112.16 Mb | Chr 9: 50.47 – 50.49 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Interleukin-18 (IL-18), also known as interferon-gamma inducing factor is a
endothelial cells.[8] IL-18 can modulate both innate and adaptive immunity and its dysregulation can cause autoimmune or inflammatory diseases.[9][10]
Processing
kDa precursor with no signal peptide, which accumulates in the cell cytoplasm. Similarly to IL-1β, the IL-18 precursor is processed intracellularly by caspase 1 in the NLRP3 inflammasome into its mature biologically active molecule of 18 kDa.[12]
Receptor and signaling
IL-18
IFNγ production. Thus, IL-37 and IL-18 have opposing roles and IL-37 can modulate pro-inflammatory effects of IL-18.[16][15]
Function
IL-18 belongs to the
type II interferon that plays an important role in activating the macrophages or other cells. The combination of IL-18 and IL-12 has been shown to inhibit IL-4 dependent IgE and IgG1 production and enhance IgG2a production in B cells.[17] Importantly, without IL-12 or IL-15, IL-18 does not induce IFNγ production, but plays an important role in the differentiation of naive T cells into Th2 cells and stimulates mast cells and basophils to produce IL-4, IL-13, and chemical mediators such as histamine.[18]
Clinical significance
Apart from its physiological role, IL-18 is also able to induce severe
autoimmune disorders.[19] High levels of IL18 have also been described in essential hypertensive subjects[20]
Endometrial
IL-18 receptor mRNA and the ratio of IL-18 binding protein to interleukin 18 is significantly increased in adenomyosis patients in comparison to normal people, indicating a role in its pathogenesis.[21]
IL-18 has been implicated as an inflammatory mediator of
interferon-gamma.[22]
IL-18 has also been found to increase the
amyloid-beta production in human neuron cells.[23]
IL-18 is also associated with urine protein excretion which means that it can be marker for assessing the progression of diabetic nephropathy.[24][25] This interleukin was also significantly elevated in patients with microalbuminuria and macroalbuminuria when it was compared with healthy people and patients with diabetes which have normoalbuminuria.[26]
IL-18 is involved in the neuroinflammatory response after intracerebral hemorrhage.[27]
The
systemic lupus erythematosus and to be a possible "key factor in the expression of the IL18 gene."[19]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000150782 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039217 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 4323405.
- PMID 9693051.
- PMID 2492265.
- PMID 30717382.
- PMID 31231372.
- S2CID 25636657.
- S2CID 9115114.
- S2CID 85955985.
- PMID 10525448.
- PMID 29247988.
- ^ PMID 29805973.
- PMID 19699681.[permanent dead link]
- ^ "Entrez Gene: IL18 interleukin 18 (interferon-gamma-inducing factor)".
- PMID 30717382.
- ^ )
- .
- PMID 19394601.
- PMID 20586818.
- PMID 22898493.
- PMID 26517838.
- PMID 16306550.
- PMID 31218128.
- S2CID 85495400.
Further reading
- Biet F, Locht C, Kremer L (March 2002). "Immunoregulatory functions of interleukin 18 and its role in defense against bacterial pathogens". Journal of Molecular Medicine. 80 (3): 147–62. S2CID 34752902.
- Nakanishi K (February 2002). "[Regulation of Th1 and Th2 immune responses by IL-18]". Kekkaku. 77 (2): 87–93. PMID 11905033.
- Reddy P, Ferrara JL (June 2003). "Role of interleukin-18 in acute graft-vs-host disease". The Journal of Laboratory and Clinical Medicine. 141 (6): 365–71. PMID 12819633.
- Kanai T, Uraushihara K, Totsuka T, Okazawa A, Hibi T, Oshima S, et al. (June 2003). "Macrophage-derived IL-18 targeting for the treatment of Crohn's disease". Current Drug Targets. Inflammation and Allergy. 2 (2): 131–6. PMID 14561165.
- Matsui K, Tsutsui H, Nakanishi K (December 2003). "Pathophysiological roles for IL-18 in inflammatory arthritis". Expert Opinion on Therapeutic Targets. 7 (6): 701–24. S2CID 25093203.
- Yoshimoto T, Nakanishi K (June 2006). "Roles of IL-18 in basophils and mast cells". Allergology International. 55 (2): 105–13. PMID 17075246.
- Orozco A, Gemmell E, Bickel M, Seymour GJ (July 2007). "Interleukin 18 and periodontal disease". Journal of Dental Research. 86 (7): 586–93. S2CID 26910667.
External links
- Overview of all the structural information available in the PDB for UniProt: Q14116 (Interleukin-18) at the PDBe-KB.
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