Interleukin 1 receptor antagonist

Interleukin 1 receptor antagonist
Rendering of 1ILR​
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1ILR​, 1ILT​, 1IRA​, 1IRP​, 1ITN​, 2IRT​
Identifiers
Symbols	IL1RN ; DIRA; ICIL-1RA; IL-1RN; IL-1ra; IL-1ra3; IL1F3; IL1RA; IRAP; MVCD4
External IDs	OMIM: 147679 MGI: 96547 HomoloGene: 11163 GeneCards: IL1RN Gene
Gene ontology Molecular function • cytokine activity • interleukin-1 receptor binding • interleukin-1, Type I receptor binding • interleukin-1, Type II receptor binding • interleukin-1 receptor antagonist activity • interleukin-1 Type I receptor antagonist activity • interleukin-1 Type II receptor antagonist activity Cellular component • extracellular space • intracellular • cytoplasm • plasma membrane • extracellular exosome Biological process • fever generation • negative regulation of cytokine-mediated signaling pathway • inflammatory response to antigenic stimulus • chronic inflammatory response to antigenic stimulus • lipid metabolic process • acute-phase response • immune response • female pregnancy • memory • negative regulation of glutamate secretion • response to activity • sensory perception of pain • carboxylic acid metabolic process • insulin secretion • negative regulation of cell migration • response to lipopolysaccharide • negative regulation of heterotypic cell-cell adhesion • response to drug • response to starvation • negative regulation of apoptotic process • positive regulation of JUN kinase activity • negative regulation of membrane potential • response to glucocorticoid • response to interleukin-1 • response to interleukin-4 • cellular response to norepinephrine stimulus • negative regulation of interleukin-1-mediated signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3557	16181
Ensembl	ENSG00000136689	ENSMUSG00000026981
UniProt	P18510	P25085
RefSeq (mRNA)	NM_000577	NM_001039701
RefSeq (protein)	NP_000568	NP_001034790
Location (UCSC)	Chr 2: 113.11 – 113.13 Mb	Chr 2: 24.34 – 24.35 Mb
PubMed search

The interleukin-1 receptor antagonist (IL-1RA) is a protein that in humans is encoded by the IL1RN gene.^[1][2]

IL-1RA was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories.^[3] IL-1RA, is an agent that binds non-productively to the cell surface interleukin-1 receptor (IL-1R). IL-1R is the same receptor that binds interleukin 1 (IL-1). Hence IL-1RA prevents IL-1 from sending a signal to that cell.

Function

IL-1RA is a member of the interleukin 1 cytokine family. IL1Ra is secreted by various types of cells including immune cells, epithelial cells, and adipocytes, and is a natural inhibitor of the pro-inflammatory effect of IL1β.^[4] This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.^[5]

Clinical significance

A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures^[6] and gastric cancer.^[7]

Mutations in the IL1RN gene results in a rare disease called deficiency of the interleukin-1–receptor antagonist (DIRA).^[8] Variants of the IL1RN gene is also associated with risk of schizophrenia.^[9][10] Elevated levels of IL1RN has been found in serum of schizophrenia patients.^[11]

An interleukin 1 receptor antagonist is used in the treatment of rheumatoid arthritis, an autoimmune disease in which IL-1 plays a key role. It is commercially produced as anakinra, which is a human recombinant form of IL-1RA. In terms of protein similarities, IL-1β is more closely related to IL-1RA than it is to IL- 1α. The amino acids that are identical between mature human IL-1α and mature IL-1β is 22% while it is 26% when comparing IL-1β to IL-1RA and only 18% when comparing IL-1α to IL-1RA.^[3]

Use in horses

Interleukin 1 receptor antagonist is used in horses for the treatment of equine lameness secondary to joint injury.

References

1. Steinkasserer A, Spurr NK, Cox S, Jeggo P, Sim RB (July 1992). "The human IL-1 receptor antagonist gene (IL1RN) maps to chromosome 2q14-q21, in the region of the IL-1 alpha and IL-1 beta loci". Genomics 13 (3): 654–7. doi:10.1016/0888-7543(92)90137-H. PMID 1386337.
2. Patterson D, Jones C, Hart I, Bleskan J, Berger R, Geyer D, Eisenberg SP, Smith MF, Arend WP (January 1993). "The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region". Genomics 15 (1): 173–6. doi:10.1006/geno.1993.1025. PMID 8432529.
3. Dinarello CA (December 1994). "The interleukin-1 family: 10 years of discovery". FASEB J. 8 (15): 1314–25. PMID 8001745.
4. Perrier S, Darakhshan F, Hajduch E (November 2006). "IL-1 receptor antagonist in metabolic diseases: Dr Jekyll or Mr Hyde?". FEBS Lett. 580 (27): 6289–94. doi:10.1016/j.febslet.2006.10.061. PMID 17097645.
5. "Entrez Gene: IL1RN interleukin 1 receptor antagonist".
6. Langdahl BL, Løkke E, Carstens M, Stenkjaer LL, Eriksen EF (March 2000). "Osteoporotic fractures are associated with an 86-base pair repeat polymorphism in the interleukin-1--receptor antagonist gene but not with polymorphisms in the interleukin-1beta gene". J. Bone Miner. Res. 15 (3): 402–14. doi:10.1359/jbmr.2000.15.3.402. PMID 10750554.
7. El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, Herrera J, Lissowska J, Yuan CC, Rothman N, Lanyon G, Martin M, Fraumeni JF, Rabkin CS (March 2000). "Interleukin-1 polymorphisms associated with increased risk of gastric cancer". Nature 404 (6776): 398–402. doi:10.1038/35006081. PMID 10746728.
8. Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J, van Royen-Kerkhoff A, Laxer R, Tedgård U, Cowen EW, Pham TH, Booty M, Estes JD, Sandler NG, Plass N, Stone DL, Turner ML, Hill S, Butman JA, Schneider R, Babyn P, El-Shanti HI, Pope E, Barron K, Bing X, Laurence A, Lee CC, Chapelle D, Clarke GI, Ohson K, Nicholson M, Gadina M, Yang B, Korman BD, Gregersen PK, van Hagen PM, Hak AE, Huizing M, Rahman P, Douek DC, Remmers EF, Kastner DL, Goldbach-Mansky R (June 2009). "An Autoinflammatory Disease with Deficiency of the Interleukin-1–Receptor Antagonist". N. Engl. J. Med. 360 (23): 2426–37. doi:10.1056/NEJMoa0807865. PMC 2876877. PMID 19494218.
9. Kim SJ, Lee HJ, Koo HG, Kim JW, Song JY, Kim MK, Shin DH, Jin SY, Hong MS, Park HJ, Yoon SH, Park HK, Chung JH (September 2004). "Impact of IL-1 receptor antagonist gene polymorphism on schizophrenia and bipolar disorder". Psychiatr. Genet. 14 (3): 165–7. doi:10.1097/00041444-200409000-00009. PMID 15318032.
10. Zanardini R, Bocchio-Chiavetto L, Scassellati C, Bonvicini C, Tura GB, Rossi G, Perez J, Gennarelli M (2003). "Association between IL-1beta -511C/T and IL-1RA (86bp)n repeats polymorphisms and schizophrenia". J Psychiatr Res 37 (6): 457–62. doi:10.1016/S0022-3956(03)00072-4. PMID 14563376.
11. Hope S, Melle I, Aukrust P, Steen NE, Birkenaes AB, Lorentzen S, Agartz I, Ueland T, Andreassen OA (November 2009). "Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor". Bipolar Disord 11 (7): 726–34. doi:10.1111/j.1399-5618.2009.00757.x. PMID 19839997.

Further reading

• Arend WP, Malyak M, Guthridge CJ, Gabay C (1998). "Interleukin-1 receptor antagonist: role in biology". Annu. Rev. Immunol. 16: 27–55. doi:10.1146/annurev.immunol.16.1.27. PMID 9597123.
• Adcock IM, Ito K (2000). "Molecular mechanisms of corticosteroid actions". Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo 55 (3): 256–66. PMID 10948677.
• Arend WP (2003). "The balance between IL-1 and IL-1Ra in disease". Cytokine Growth Factor Rev. 13 (4–5): 323–40. doi:10.1016/S1359-6101(02)00020-5. PMID 12220547.
• Sehouli J, Mustea A, Könsgen D, et al. (2003). "Polymorphism of IL-1 receptor antagonist gene: role in cancer". Anticancer Res. 22 (6A): 3421–4. PMID 12530098.
• Kamangar F, Cheng C, Abnet CC, Rabkin CS (2007). "Interleukin-1B polymorphisms and gastric cancer risk--a meta-analysis". Cancer Epidemiol. Biomarkers Prev. 15 (10): 1920–8. doi:10.1158/1055-9965.EPI-06-0267. PMID 17035400.

External links

• Interleukin 1 Receptor Antagonist Protein at the US National Library of Medicine Medical Subject Headings (MeSH)