The IL-1 receptor antagonist (IL-1RA) was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories.[1] IL-1RA, is an agent which binds to the same receptor on the cell surface as IL-1 (IL1R), and thus prevents IL-1 from sending a signal to that cell.
Mutations in the IL1RN gene, which encodes this protein, results in a rare disease called deficiency of the interleukin-1–receptor antagonist (DIRA) [2].
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.[1]
The protein encoded by this gene is a member of the interleukin 1 cytokine family. 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. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.[3]
References
- ^ a b C.A. Dinarello. The interleukin-1 family: 10 years of discovery. FASEB Journal. Volume 8, Issue 15, 1994, pages 1314-25. PMID 8001745
- ^ I. Aksentijevich, S. L. Masters, P. J. Ferguson et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. Volume 360, Issue 23, 2009, pages 2426-37. PMID 19494218
- ^ "Entrez Gene: IL1RN interleukin 1 receptor antagonist". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3557.
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.
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1ilr: CRYSTAL STRUCTURE OF THE INTERLEUKIN-1 RECEPTOR ANTAGONIST
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1ira: COMPLEX OF THE INTERLEUKIN-1 RECEPTOR WITH THE INTERLEUKIN-1 RECEPTOR ANTAGONIST (IL1RA)
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1irp: SOLUTION STRUCTURE OF HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN
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