Antagonist interleukin-1 receptora

Interleukin 1 receptor antagonist
Interleukin 1 receptor antagonist
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
Ontologija gena
Molekularna funkcija	• aktivnost interleukin-1 receptor antagonista; • proteinsko vezivanje;
Celularna komponenta	• ekstracelularni region; • ekstracelularni prostor; • intracelularni prostor;
Biološki proces	• inflamatorni respons; • imunski respons;
Pregled RNK izražavanja
	podaci
Ortolozi
Vrsta	Čovek
Entrez	3557
Ensembl	ENSG00000136689
UniProt	P18510
RefSeq (mRNA)	NM_000577
RefSeq (protein)	NP_000568
Lokacija (UCSC)	Chr 2:; 113.59 - 113.61 Mb
PubMed pretraga	[1]

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

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 približno 400 kb na hromozomu 2. Četiri alternativno splajsovane transkriptne varijante koje kodiraju jedinstvene izoforme su bile utvrđene.^[4]

Klinički značaj

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

^ Steinkasserer A, Spurr NK, Cox S, Jeggo P, Sim RB (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. PMID 1386337. doi:10.1016/0888-7543(92)90137-H.
^ Patterson D, Jones C, Hart I, Bleskan J, Berger R, Geyer D, Eisenberg SP, Smith MF, Arend WP (1993). „The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region”. Genomics. 15 (1): 173—6. PMID 8432529. doi:10.1006/geno.1993.1025.
^ ^а ^б Dinarello CA (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 (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. PMID 10750554. doi:10.1359/jbmr.2000.15.3.402.
^ 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 (2000). „Interleukin-1 polymorphisms associated with increased risk of gastric cancer”. Nature. 404 (6776): 398—402. PMID 10746728. doi:10.1038/35006081.
^ 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 (2009). „An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist”. N. Engl. J. Med. 360 (23): 2426—37. PMC 2876877 . PMID 19494218. doi:10.1056/NEJMoa0807865.
^ 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 (2004). „Impact of IL-1 receptor antagonist gene polymorphism on schizophrenia and bipolar disorder”. Psychiatr. Genet. 14 (3): 165—7. PMID 15318032. doi:10.1097/00041444-200409000-00009.
^ 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. PMID 14563376. doi:10.1016/S0022-3956(03)00072-4.
^ Hope S, Melle I, Aukrust P, Steen NE, Birkenaes AB, Lorentzen S, Agartz I, Ueland T, Andreassen OA (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. PMID 19839997. doi:10.1111/j.1399-5618.2009.00757.x.

Literatura

Arend WP, Malyak M, Guthridge CJ, Gabay C (1998). „Interleukin-1 receptor antagonist: role in biology.”. Annu. Rev. Immunol. 16: 27—55. PMID 9597123. doi:10.1146/annurev.immunol.16.1.27.
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. PMID 12220547. doi:10.1016/S1359-6101(02)00020-5.
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. PMID 17035400. doi:10.1158/1055-9965.EPI-06-0267.

Spoljašnje veze

Interleukin+1+Receptor+Antagonist+Protein на US National Library of Medicine Medical Subject Headings (MeSH)

[pmid1386337-1] Steinkasserer A, Spurr NK, Cox S, Jeggo P, Sim RB (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. PMID 1386337. doi:10.1016/0888-7543(92)90137-H.

[pmid8432529-2] Patterson D, Jones C, Hart I, Bleskan J, Berger R, Geyer D, Eisenberg SP, Smith MF, Arend WP (1993). „The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region”. Genomics. 15 (1): 173—6. PMID 8432529. doi:10.1006/geno.1993.1025.

[dinarello-3] а ^б Dinarello CA (1994). „The interleukin-1 family: 10 years of discovery”. FASEB J. 8 (15): 1314—25. PMID 8001745.

[entrez-4] „Entrez Gene: IL1RN interleukin 1 receptor antagonist”.

[pmid10750554-5] Langdahl BL, Løkke E, Carstens M, Stenkjaer LL, Eriksen EF (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. PMID 10750554. doi:10.1359/jbmr.2000.15.3.402.

[pmid10746728-6] 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 (2000). „Interleukin-1 polymorphisms associated with increased risk of gastric cancer”. Nature. 404 (6776): 398—402. PMID 10746728. doi:10.1038/35006081.

[pmid19494218-7] 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 (2009). „An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist”. N. Engl. J. Med. 360 (23): 2426—37. PMC 2876877 . PMID 19494218. doi:10.1056/NEJMoa0807865.

[pmid15318032-8] 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 (2004). „Impact of IL-1 receptor antagonist gene polymorphism on schizophrenia and bipolar disorder”. Psychiatr. Genet. 14 (3): 165—7. PMID 15318032. doi:10.1097/00041444-200409000-00009.

[pmid14563376-9] 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. PMID 14563376. doi:10.1016/S0022-3956(03)00072-4.

[pmid19839997-10] Hope S, Melle I, Aukrust P, Steen NE, Birkenaes AB, Lorentzen S, Agartz I, Ueland T, Andreassen OA (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. PMID 19839997. doi:10.1111/j.1399-5618.2009.00757.x.

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