Antagonist interleukin-1 receptora
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| Interleukin 1 receptor antagonist | |||||||||||
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| Dostupne strukture | |||||||||||
| 1ilr, 1ilt, 1ira, 1irp, 2irt | |||||||||||
| Identifikatori | |||||||||||
| Simboli | IL1RN; IL1RA; ICIL-1RA; IL-1ra3; IL1F3; IRAP; MGC10430 | ||||||||||
| Vanjski ID | OMIM: 147679 MGI: 96547 HomoloGene: 11163 GeneCards: IL1RN Gene | ||||||||||
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| Pregled RNK izražavanja | |||||||||||
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| Ortolozi | |||||||||||
| Vrsta | Čovek | Miš | |||||||||
| Entrez | 3557 | 16181 | |||||||||
| Ensembl | ENSG00000136689 | ENSMUSG00000026981 | |||||||||
| UniProt | P18510 | Q3TBV5 | |||||||||
| RefSeq (mRNA) | NM_000577 | NM_001039701 | |||||||||
| RefSeq (protein) | NP_000568 | NP_001034790 | |||||||||
| Lokacija (UCSC) | Chr 2: 113.59 - 113.61 Mb | Chr 2: 24.16 - 24.17 Mb | |||||||||
| PubMed pretraga | [1] | [2] | |||||||||
Antagonist interleukin-1 receptora (IL-1RA) je protein koji je kod ljudi kodiran IL1RN genom.[1][2]
IL-1RA antagonist se ranije zvao IL-1 inhibitor. Njega su nezavisno otkrile dve laboratorije 1984 godine.[3] IL-1RA, se vezuje za interleukin-1 receptor (IL-1R) na površini ćelija. Za IL-1R se isto tako vezuje interleukin 1 (IL-1). IL-1RA sprečava IL-1 da pošalje signal.
Funkcija[uredi | uredi kod]
IL-1RA je član interleukin 1 citokin familije. Ovaj protein inhibira aktivnosti interleukina 1, alfa (IL1A) i interleukina 1, beta (IL1B), i modulira niz interleukin 1 zavisnih imunskih i inflamatornih odgovora. Ovaj gene i pet drugih blisko srodnih citokin gena formiraju genski klaster koji obuhvata aproksimativno 400 kb na hromozomu 2. Četiri alternativno splajsovane transkriptne varijante koje kodiraju jedinstvene izoforme su bile utvrđene.[4]
Klinički značaj[uredi | uredi kod]
Za polimorfizam ovog gena se smatra da je vezan za povećani rizik osteoporoznih fraktura[5] i gastričnog karcinoma.[6]
Mutacije u IL1RN genu rezultuju u retkoj bolesti koja se zove nedostatak antagonista interleukin-1 receptora (DIRA).[7] Varijante IL1RN gena su takođe asocirane sa rizikom od shizofrenije.[8][9] Povišeni IL1RN nivoi su nađeni u serumu obolelih od shizofrenije.[10]
Interleukin 1 receptor antagonist je korišćen u tretmanu reumatoidnog artritisa, autoimune bolesti u kojoj IL-1 igra ključnu ulogu. On se komercijalno proizvodi kao anakinra, što je ljudska rekombinantna forma L-1RA. U pogledu proteinske sličnosti, IL-1β srodniji sa IL-1RA nego IL- 1α.[3]
Reference[uredi | uredi kod]
- ↑ 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.
- ↑ 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.
- ↑ 3,0 3,1 Dinarello CA (December 1994). „The interleukin-1 family: 10 years of discovery”. FASEB J. 8 (15): 1314–25. PMID 8001745.
- ↑ „Entrez Gene: IL1RN interleukin 1 receptor antagonist”.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
Literatura[uredi | uredi kod]
- 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.
Spoljašnje veze[uredi | uredi kod]
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