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词条 Interleukin 1 receptor antagonist
释义

  1. Function

  2. Clinical significance

     Use in horses 

  3. References

  4. Further reading

  5. External links

{{Infobox_gene}}

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), the same receptor that binds interleukin 1 (IL-1), preventing 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]

A recombinant, slightly modified version of interleukin 1 receptor antagonist called anakinra is used in the treatment of rheumatoid arthritis, an autoimmune disease in which IL-1 plays a key role.[12] Anakinra differs from native human IL-1Ra in that it has the addition of a single methionine residue at its amino terminus [13]

Use in horses

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

References

1. ^{{cite journal |vauthors=Steinkasserer A, Spurr NK, Cox S, Jeggo P, Sim RB | title = 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 | journal = Genomics | volume = 13 | issue = 3 | pages = 654–7 |date=July 1992 | pmid = 1386337 | doi = 10.1016/0888-7543(92)90137-H| url = }}
2. ^{{cite journal |vauthors=Patterson D, Jones C, Hart I, Bleskan J, Berger R, Geyer D, Eisenberg SP, Smith MF, Arend WP | title = The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region | journal = Genomics | volume = 15 | issue = 1 | pages = 173–6 |date=January 1993 | pmid = 8432529 | doi = 10.1006/geno.1993.1025 | url = }}
3. ^{{cite journal | author = Dinarello CA | title = The interleukin-1 family: 10 years of discovery | journal = FASEB J. | volume = 8 | issue = 15 | pages = 1314–25 |date=December 1994 | pmid = 8001745 | doi = 10.1096/fasebj.8.15.8001745| url = }}
4. ^{{cite journal |vauthors=Perrier S, Darakhshan F, Hajduch E | title = IL-1 receptor antagonist in metabolic diseases: Dr Jekyll or Mr Hyde? | journal = FEBS Lett. | volume = 580 | issue = 27 | pages = 6289–94 |date=November 2006 | pmid = 17097645 | doi = 10.1016/j.febslet.2006.10.061 }}
5. ^{{cite web | title = Entrez Gene: IL1RN interleukin 1 receptor antagonist| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3557| accessdate = }}
6. ^{{cite journal |vauthors=Langdahl BL, Løkke E, Carstens M, Stenkjaer LL, Eriksen EF | title = 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 | journal = J. Bone Miner. Res. | volume = 15 | issue = 3 | pages = 402–14 |date=March 2000 | pmid = 10750554 | doi = 10.1359/jbmr.2000.15.3.402 | url = }}
7. ^{{cite journal |vauthors=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 | title = Interleukin-1 polymorphisms associated with increased risk of gastric cancer | journal = Nature | volume = 404 | issue = 6776 | pages = 398–402 |date=March 2000 | pmid = 10746728 | doi = 10.1038/35006081 | url = }}
8. ^{{cite journal |vauthors=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 | title = An Autoinflammatory Disease with Deficiency of the Interleukin-1–Receptor Antagonist | journal = N. Engl. J. Med. | volume = 360 | issue = 23 | pages = 2426–37 |date=June 2009 | pmid = 19494218 | doi = 10.1056/NEJMoa0807865 | url = | pmc = 2876877 }}
9. ^{{cite journal |vauthors=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 | title = Impact of IL-1 receptor antagonist gene polymorphism on schizophrenia and bipolar disorder | journal = Psychiatr. Genet. | volume = 14 | issue = 3 | pages = 165–7 |date=September 2004 | pmid = 15318032 | doi = 10.1097/00041444-200409000-00009| url = }}
10. ^{{cite journal |vauthors=Zanardini R, Bocchio-Chiavetto L, Scassellati C, Bonvicini C, Tura GB, Rossi G, Perez J, Gennarelli M | title = Association between IL-1beta -511C/T and IL-1RA (86bp)n repeats polymorphisms and schizophrenia | journal = J Psychiatr Res | volume = 37 | issue = 6 | pages = 457–62 | year = 2003 | pmid = 14563376 | doi = 10.1016/S0022-3956(03)00072-4| url = }}
11. ^{{cite journal |vauthors=Hope S, Melle I, Aukrust P, Steen NE, Birkenaes AB, Lorentzen S, Agartz I, Ueland T, Andreassen OA | title = Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor | journal = Bipolar Disord | volume = 11 | issue = 7 | pages = 726–34 |date=November 2009 | pmid = 19839997 | doi = 10.1111/j.1399-5618.2009.00757.x | url = | hdl = 10852/34620 }}
12. ^{{cite journal | vauthors = Mertens M, Singh JA | title = Anakinra for rheumatoid arthritis | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD005121 | date = January 2009 | pmid = 19160248 | doi = 10.1002/14651858.CD005121.pub3 }}
13. ^{{cite web | title = Kineret (anakinra) injection, for subcutaneous use | url = http://www.kineretrx.com/pdf/Full-Prescribing-Information-English.pdf | publisher = Swedish Orphan Biovitrum }}

Further reading

{{refbegin | 2}}
  • {{cite journal |vauthors=Arend WP, Malyak M, Guthridge CJ, Gabay C |title=Interleukin-1 receptor antagonist: role in biology |journal=Annu. Rev. Immunol. |volume=16 |issue= |pages= 27–55 |year= 1998 |pmid= 9597123 |doi= 10.1146/annurev.immunol.16.1.27 }}
  • {{cite journal |vauthors=Adcock IM, Ito K |title=Molecular mechanisms of corticosteroid actions |journal=Monaldi Archives for Chest Disease |volume=55 |issue= 3 |pages= 256–66 |year= 2000 |pmid= 10948677 |doi= }}
  • {{cite journal | author=Arend WP |title=The balance between IL-1 and IL-1Ra in disease |journal=Cytokine Growth Factor Rev. |volume=13 |issue= 4–5 |pages= 323–40 |year= 2003 |pmid= 12220547 |doi=10.1016/S1359-6101(02)00020-5 }}
  • {{cite journal |vauthors=Sehouli J, Mustea A, Könsgen D, etal |title=Polymorphism of IL-1 receptor antagonist gene: role in cancer |journal=Anticancer Res. |volume=22 |issue= 6A |pages= 3421–4 |year= 2003 |pmid= 12530098 |doi= }}
  • {{cite journal |vauthors=Kamangar F, Cheng C, Abnet CC, Rabkin CS |title=Interleukin-1B polymorphisms and gastric cancer risk--a meta-analysis |journal=Cancer Epidemiol. Biomarkers Prev. |volume=15 |issue= 10 |pages= 1920–8 |year= 2007 |pmid= 17035400 |doi= 10.1158/1055-9965.EPI-06-0267 }}
{{refend}}

External links

  • {{MeshName|Interleukin+1+Receptor+Antagonist+Protein}}
{{PDB Gallery|geneid=3557}}{{Interleukins}}{{Interleukin receptor modulators}}

1 : Cytokines
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