Antagonista do receptor de interleucina 1

IL1RN
Estruturas dispoñibles
PDB	Buscar ortólogos: PDBe, RCSB Lista de códigos PDB 1ILR, 1ILT, 1IRA, 1IRP, 2IRT ;
Identificadores
Símbolos	IL1RN (HGNC: 6000) DIRA, ICIL-1RA, IL-1RN, IL-1ra, IL-1ra3, IL1F3, IL1RA, IRAP, MVCD4, antgonista do receptor de interleucina 1
Identificadores; externos	OMIM: 147679 ; MGI: 96547 ; HomoloGene: 11163 ; EBI: IL1RN; GeneCards: Xene IL1RN; UniProt: IL1RN;
Locus	Cr. 2 q14.1
Ontoloxía Xénica	Referencias: AmiGO / QuickGO
	Referencias: AmiGO / QuickGO
Padrón de expresión de ARNm
	Máis información
Ortólogos
Especies
Humano	Rato
Entrez
3557	16181
Ensembl
Véxase HS	Véxase MM
UniProt
P18510	P25085
RefSeq; (ARNm)
NM_000577	NM_001039701
RefSeq; (proteína) NCBI
NP_000568	NP_001034790
Localización (UCSC)
Cr. 2:; 113.11 – 113.13 Mb	Cr. 2:; 24.34 – 24.35 Mb
PubMed (Busca)
3557 ;	16181

O antagonista do receptor de interleucina 1 (IL-1RA) é unha proteína que nos humanos está codificada no xene IL1RN do cromosoma 2.^[1]^[2]

O IL-1RA foi inicialmente denominado inhibidor de IL-1 e foi descuberto por separado en 1984 por dous laboratorios independentes.^[3] O IL-1RA é un axente que se une non produtivamente á superficie celular no receptor de interleucina-1 (IL-1R), o mesmo receptor que se une á interleucina 1 (IL-1), impedindo que a IL-1 envíe un sinal a esa célula.

Función

O IL-1RA é un membro da familia de citocinas da interleucina 1. O IL1RA é segregada por varios tipos de células incluíndo as células inmunes, células epiteliais e adipocitos e é un inhibidor natural do efecto proinflamatorio da IL1β.^[4] Esta proteína inhibe as actividades da interleucina 1 alfa (IL1A) e a interleucina 1 beta (IL1B), e modula unha variedade de respostas inmunes e inflamatorias relacionadas coa interleucina 1. Este xene e outros cinco estreitamente relacionados forman un cluster de xenes que abrangue aproximadamente 400 kb no cromosoma 2. Descubríronse catro variantes de transcrición resultado de empalme alternativo que codifican distintas isoformas.^[5]

Importancia clínica

Un polimorfismo deste xene está asociado co incremento do risco de sufrir fracturas osteoporóticas^[6] e cancro gástrico.^[7]

As mutacións no xene IL1RN orixinan unha enfermidade rara chamada deficiencia do antagonista do receptor de interleucina 1.^[8] A variante do xene IL1RN está tamén asociada co risco de esquizofenia.^[9]^[10] Encontráronse niveis elevados de IL1RN no soro sanguíneo de pacientes de esquizofrenia.^[11]

Unha versión recombinante, lixeiramente modificada do antagonista do receptor de interleucina 1 chamada anakinra utilízase no tratamento da artrite reumatoide, unha enfermidade autoinmune na cal a IL-1 xoga un papel clave.^[12] A anakinra difire do IL-1RA humano nativo en que ten un só residuo de metionina adicional no seu amino-terminal.^[13]

Uso en cabalos

O antagonista do receptor da interleucina 1 utilízase en cabalos para o tratamento da coxeira equina resultante de lesións articulares e de tecidos brandos.

Notas

↑ 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. 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 (January 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 CA (December 1994). "The interleukin-1 family: 10 years of discovery". FASEB J. 8 (15): 1314–25. PMID 8001745. doi:10.1096/fasebj.8.15.8001745.
↑ 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. PMID 17097645. doi:10.1016/j.febslet.2006.10.061.
↑ "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. 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 (March 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 (June 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 (September 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 (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. PMID 19839997. doi:10.1111/j.1399-5618.2009.00757.x. hdl:10852/34620.
↑ Mertens M, Singh JA (January 2009). "Anakinra for rheumatoid arthritis". The Cochrane Database of Systematic Reviews (1): CD005121. PMID 19160248. doi:10.1002/14651858.CD005121.pub3.
↑ "Kineret (anakinra) injection, for subcutaneous use" (PDF). Swedish Orphan Biovitrum.

Véxase tamén

Outros artigos

Bibliografía

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 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.

Ligazóns externas

Interleukin 1 Receptor Antagonist Protein Medical Subject Headings (MeSH) na Biblioteca Nacional de Medicina dos EUA.

[pmid1386337-1] 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. 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 (January 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] Dinarello CA (December 1994). "The interleukin-1 family: 10 years of discovery". FASEB J. 8 (15): 1314–25. PMID 8001745. doi:10.1096/fasebj.8.15.8001745.

[pmid17097645-4] 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. PMID 17097645. doi:10.1016/j.febslet.2006.10.061.

[entrez-5] "Entrez Gene: IL1RN interleukin 1 receptor antagonist".

[pmid10750554-6] 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. PMID 10750554. doi:10.1359/jbmr.2000.15.3.402.

[pmid10746728-7] 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. PMID 10746728. doi:10.1038/35006081.

[pmid19494218-8] 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. PMC 2876877. PMID 19494218. doi:10.1056/NEJMoa0807865.

[pmid15318032-9] 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. PMID 15318032. doi:10.1097/00041444-200409000-00009.

[pmid14563376-10] 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. PMID 14563376. doi:10.1016/S0022-3956(03)00072-4.

[pmid19839997-11] 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. PMID 19839997. doi:10.1111/j.1399-5618.2009.00757.x. hdl:10852/34620.

[12] Mertens M, Singh JA (January 2009). "Anakinra for rheumatoid arthritis". The Cochrane Database of Systematic Reviews (1): CD005121. PMID 19160248. doi:10.1002/14651858.CD005121.pub3.

[prescribing_information-13] "Kineret (anakinra) injection, for subcutaneous use" (PDF). Swedish Orphan Biovitrum.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]