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Gene Review

IL1R1  -  interleukin 1 receptor, type I

Homo sapiens

Synonyms: CD121 antigen-like family member A, CD121A, D2S1473, IL-1R-1, IL-1R-alpha, ...
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Disease relevance of IL1R1

  • We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation [1].
  • Modulation of endogenous IL-1 beta and IL-1 receptor antagonist results in opposing effects on HIV expression in chronically infected monocytic cells [2].
  • Mucosal imbalance of IL-1 and IL-1 receptor antagonist in inflammatory bowel disease. A novel mechanism of chronic intestinal inflammation [3].
  • Our laboratory has previously demonstrated that another anti-inflammatory cytokine, IL-1 receptor antagonist (IRAP) is produced and secreted by human bronchogenic carcinomas [4].
  • The present findings suggest that the dysregulation of IL-1/IL-1-R system relates to immunological dysfunction in endometriosis [5].

Psychiatry related information on IL1R1


High impact information on IL1R1

  • A new member of the IL-1 receptor family highly expressed in hippocampus and involved in X-linked mental retardation [11].
  • These results indicate katanin's activities are segregated into a subunit (p60) that possesses enzymatic activity and a subunit (p80) that targets the enzyme to the centrosome [12].
  • A region in the intracellular domain of TLR2 with homology to a portion of the interleukin (IL)-1 receptor that is implicated in the activation of the IL-1-receptor-associated kinase is required for this response [13].
  • The binding of IL-1alpha or IL-1beta to IL1R is an early step in IL-1 signal transduction and blocking this interaction may therefore be a useful target for the development of new drugs [14].
  • The mature translation product of the cDNA has been expressed in Escherichia coli and was an active competitive inhibitor of the binding of IL-1 to the T-cell/fibroblast form of the IL-1 receptor [15].

Chemical compound and disease context of IL1R1

  • Associations were found between susceptibility to septic shock and allele*2 carriage for both IL-1beta-511*C/T and TNF-alpha-308*G/A, and also between poor prognosis and allele*2 carriage in both IL-1 receptor antagonist second intron various number of tandem repeats polymorphism (IL-1raRN*1-5) and TNF-alpha-308*G/A [16].
  • Regulation by rho family GTPases of IL-1 receptor induced signaling: C3-like chimeric toxin and Clostridium difficile toxin B inhibit signaling pathways involved in IL-2 gene expression [17].
  • It has been suggested that the IL-1 receptor antagonist could be used to inhibit decidual prostaglandin synthesis and thereby prevent preterm labor, but this report shows that caution should be exercised before using the receptor antagonist [18].
  • To investigate IL-1 binding, we have synthesized and purified histidine-tagged polypeptides corresponding to Fit-1S and the extracellular domain of the type I IL-1 receptor using a vaccinia expression system [19].
  • Cross-linkage of IL-1betaR type I, TNF-alphaR (p80), and IL-8R during hypoxia and H/R resulted in increased and subsequently decreased O2- production and degranulation [20].

Biological context of IL1R1

  • METHODS: We have studied -511 C/T and +3953 T/C polymorphisms of the IL1B gene, a HinfI polymorphism in the 5'UTR of the IL1R1 gene, and a variable number of tandem repeats (VNTR) in the intron 2 of the IL1RN gene, in 165 patients diagnosed as suffering from PDB and in 122 healthy controls [21].
  • The IL-1RI gene, IL1R1, maps to chromosome 2q12 [22].
  • IL1R1 promoter haplotypes showed no association with disease [1].
  • We have previously examined part of the IL1R1 promoter region and in the present study we further characterized the promoter region demarcating exon 1B and 1C by sequencing and mutation scanning [22].
  • The major novel finding of the study was a marked difference in the genotype frequencies for the IL1R1 Hinfl SNP in those with current or previous evidence of H. pylori compared to those without [23].

Anatomical context of IL1R1


Associations of IL1R1 with chemical compounds


Physical interactions of IL1R1

  • The interleukin 1 (IL-1) receptor antagonist (IL-1RN) is a naturally occurring anti-inflammatory agent that binds to the IL-1 receptor but does not possess agonist activity [33].
  • The expression of IL 1 receptor (IL 1R) on myeloma cells was also analyzed using a binding assay with 125I-labeled IL 1 alpha [34].
  • Proteasome inhibitors block the degradation of phosphorylated IRAK and correspondingly increase the amount of IL-1R1 that can be coimmunoprecipitated with IRAK [35].
  • The data show that the initial translation product from IL-1 beta mRNA must be processed in order to bind to the IL-1 receptor and hence express biological activity [36].
  • Dysregulation of LPS-induced Toll-like receptor 4-MyD88 complex formation and IL-1 receptor-associated kinase 1 activation in endotoxin-tolerant cells [37].

Enzymatic interactions of IL1R1

  • The recent characterization of an IL-1 receptor associated kinase (IRAK) and a continuous molecular path between this kinase and that which directly phosphorylates IkappaB would seem to all but close the basic understanding of IL-1 receptor signal transduction [38].

Regulatory relationships of IL1R1

  • Stimulation by the maximally effective concentration of IL-1 beta (10 ng/mL) was inhibited by the human IL-1 receptor antagonist (100 ng/mL; inhibitory constant, 23.0 ng/mL), which prefers type I over type II IL-1 receptors [39].
  • In order to further elucidate the mechanism by which IL-1ra binds without activating the IL-1 receptor, we have solved the crystal structure of IL-1ra at 2.0-A resolution [40].
  • The levels of IL-1beta in U87MG were significantly higher than in other glioma cell lines, and IL-1 receptor antagonist suppressed basal secretion of VEGF from U87MG [41].
  • Overexpression of TIRP activates NF-kappaB and potentiates IL-1 receptor-mediated NF-kappaB activation [42].
  • In the lymphoid aggregates, 20% of the cells contained IL-1 alpha and 70% expressed IL-1R1 [43].
  • IL1R1 has sense Alu elements in its 3'UTR region, making it susceptible to the regulation of other protein-coding or non-coding RNAs with antisense Alu elements [44].

Other interactions of IL1R1

  • The presence of circulating IL-1 receptor antagonist and soluble TNF binding proteins (TNF-R55-BP and TNF-R75-BP) were assessed [45].
  • The logarithm of the initial plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-1 receptor antagonist (ra), and plasminogen activator inhibitor (PAI)-1 correlated significantly with APACHE II scores (r2 = .67, .57, .68, .81, and .68, respectively) [46].
  • It recruits the adapter protein TRAF6 to the IL-1 receptor complex via an interaction with IL-1AcP [47].
  • Stimulation and priming of human neutrophils by IL-1 alpha and IL-1 beta: complete inhibition by IL-1 receptor antagonist and no interaction with other cytokines [48].
  • Moreover, a significant correlation was found between the peak IL-1 receptor antagonist and IL-10 levels (r = 0.91, p < 0.0001) [49].

Analytical, diagnostic and therapeutic context of IL1R1


  1. Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. Smith, A.J., Keen, L.J., Billingham, M.J., Perry, M.J., Elson, C.J., Kirwan, J.R., Sims, J.E., Doherty, M., Spector, T.D., Bidwell, J.L. Genes Immun. (2004) [Pubmed]
  2. Modulation of endogenous IL-1 beta and IL-1 receptor antagonist results in opposing effects on HIV expression in chronically infected monocytic cells. Goletti, D., Kinter, A.L., Hardy, E.C., Poli, G., Fauci, A.S. J. Immunol. (1996) [Pubmed]
  3. Mucosal imbalance of IL-1 and IL-1 receptor antagonist in inflammatory bowel disease. A novel mechanism of chronic intestinal inflammation. Casini-Raggi, V., Kam, L., Chong, Y.J., Fiocchi, C., Pizarro, T.T., Cominelli, F. J. Immunol. (1995) [Pubmed]
  4. Production of interleukin-10 by human bronchogenic carcinoma. Smith, D.R., Kunkel, S.L., Burdick, M.D., Wilke, C.A., Orringer, M.B., Whyte, R.I., Strieter, R.M. Am. J. Pathol. (1994) [Pubmed]
  5. Down-regulation of interleukin-1 receptor type 1 expression causes the dysregulated expression of CXC chemokines in endometriotic stromal cells: a possible mechanism for the altered immunological functions in endometriosis. Nishida, M., Nasu, K., Fukuda, J., Kawano, Y., Narahara, H., Miyakawa, I. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  6. Soluble interleukin-1 receptor type II levels are elevated in cerebrospinal fluid in Alzheimer's disease patients. Garlind, A., Brauner, A., Höjeberg, B., Basun, H., Schultzberg, M. Brain Res. (1999) [Pubmed]
  7. IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase. Li, S., Strelow, A., Fontana, E.J., Wesche, H. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  8. Impact of IL-1 receptor antagonist gene polymorphism on schizophrenia and bipolar disorder. Kim, S.J., Lee, H.J., Koo, H.G., Kim, J.W., Song, J.Y., Kim, M.K., Shin, D.H., Jin, S.Y., Hong, M.S., Park, H.J., Yoon, S.H., Park, H.K., Chung, J.H. Psychiatr. Genet. (2004) [Pubmed]
  9. Replication test for association of the IL-1 receptor antagonist gene, IL1RN, with attention-deficit/hyperactivity disorder. Misener, V.L., Schachar, R., Ickowicz, A., Malone, M., Roberts, W., Tannock, R., Kennedy, J.L., Pathare, T., Barr, C.L. Neuropsychobiology (2004) [Pubmed]
  10. Neonatal neurosteroid administration results in development-specific alterations in prepulse inhibition and locomotor activity: neurosteroids alter prepulse inhibition and locomotor activity. Gizerian, S.S., Moy, S.S., Lieberman, J.A., Grobin, A.C. Psychopharmacology (Berl.) (2006) [Pubmed]
  11. A new member of the IL-1 receptor family highly expressed in hippocampus and involved in X-linked mental retardation. Carrié, A., Jun, L., Bienvenu, T., Vinet, M.C., McDonell, N., Couvert, P., Zemni, R., Cardona, A., Van Buggenhout, G., Frints, S., Hamel, B., Moraine, C., Ropers, H.H., Strom, T., Howell, G.R., Whittaker, A., Ross, M.T., Kahn, A., Fryns, J.P., Beldjord, C., Marynen, P., Chelly, J. Nat. Genet. (1999) [Pubmed]
  12. Katanin, a microtubule-severing protein, is a novel AAA ATPase that targets to the centrosome using a WD40-containing subunit. Hartman, J.J., Mahr, J., McNally, K., Okawa, K., Iwamatsu, A., Thomas, S., Cheesman, S., Heuser, J., Vale, R.D., McNally, F.J. Cell (1998) [Pubmed]
  13. Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling. Yang, R.B., Mark, M.R., Gray, A., Huang, A., Xie, M.H., Zhang, M., Goddard, A., Wood, W.I., Gurney, A.L., Godowski, P.J. Nature (1998) [Pubmed]
  14. Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1beta. Vigers, G.P., Anderson, L.J., Caffes, P., Brandhuber, B.J. Nature (1997) [Pubmed]
  15. Purification, cloning, expression and biological characterization of an interleukin-1 receptor antagonist protein. Carter, D.B., Deibel, M.R., Dunn, C.J., Tomich, C.S., Laborde, A.L., Slightom, J.L., Berger, A.E., Bienkowski, M.J., Sun, F.F., McEwan, R.N. Nature (1990) [Pubmed]
  16. Cytokine-related genotypic differences in peak interleukin-6 blood levels of patients with SIRS and septic complications. Watanabe, E., Hirasawa, H., Oda, S., Shiga, H., Matsuda, K., Nakamura, M., Abe, R., Nakada, T. The Journal of trauma. (2005) [Pubmed]
  17. Regulation by rho family GTPases of IL-1 receptor induced signaling: C3-like chimeric toxin and Clostridium difficile toxin B inhibit signaling pathways involved in IL-2 gene expression. Dreikhausen, U., Varga, G., Hofmann, F., Barth, H., Aktories, K., Resch, K., Szamel, M. Eur. J. Immunol. (2001) [Pubmed]
  18. The "interleukin 1 receptor antagonist" is a partial agonist of prostaglandin synthesis by human decidual cells. Cole, O.F., Sullivan, M.H., Elder, M.G. Prostaglandins (1993) [Pubmed]
  19. Low affinity binding of interleukin-1 beta and intracellular signaling via NF-kappa B identify Fit-1 as a distant member of the interleukin-1 receptor family. Reikerstorfer, A., Holz, H., Stunnenberg, H.G., Busslinger, M. J. Biol. Chem. (1995) [Pubmed]
  20. Regulation of polymorphonuclear leukocyte cytokine receptor expression: the role of altered oxygen tensions and matrix proteins. Simms, H., D'Amico, R. J. Immunol. (1996) [Pubmed]
  21. -511 C/T IL1B gene polymorphism is associated to resistance to bisphosphonates treatment in Paget disease of bone. Corral-Gudino, L., del Pino-Montes, J., García-Aparicio, J., Corral, E., Montilla, C.A., González-Sarmiento, R. Bone (2006) [Pubmed]
  22. Characterization of new polymorphisms in the 5' UTR of the human interleukin-1 receptor type 1 (IL1R1) gene: linkage to type 1 diabetes and correlation to IL-1RI plasma level. Bergholdt, R., Larsen, Z.M., Andersen, N.A., Johannesen, J., Kristiansen, O.P., Mandrup-Poulsen, T., Nerup, J., Pociot, F. Genes Immun. (2000) [Pubmed]
  23. A functional polymorphism in the interleukin-1 receptor-1 gene is associated with increased risk of Helicobacter pylori infection but not with gastric cancer. Hartland, S., Newton, J.L., Griffin, S.M., Donaldson, P.T. Dig. Dis. Sci. (2004) [Pubmed]
  24. Interleukin 10 (IL-10) upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation. Cassatella, M.A., Meda, L., Gasperini, S., Calzetti, F., Bonora, S. J. Exp. Med. (1994) [Pubmed]
  25. The IL-1 receptor and Rho directly associate to drive cell activation in inflammation. Singh, R., Wang, B., Shirvaikar, A., Khan, S., Kamat, S., Schelling, J.R., Konieczkowski, M., Sedor, J.R. J. Clin. Invest. (1999) [Pubmed]
  26. Transplantation of transduced chondrocytes protects articular cartilage from interleukin 1-induced extracellular matrix degradation. Baragi, V.M., Renkiewicz, R.R., Jordan, H., Bonadio, J., Hartman, J.W., Roessler, B.J. J. Clin. Invest. (1995) [Pubmed]
  27. Effect of interleukin-1 (IL-1) blockade on cytokine synthesis: II. IL-1 receptor antagonist inhibits lipopolysaccharide-induced cytokine synthesis by human monocytes. Granowitz, E.V., Vannier, E., Poutsiaka, D.D., Dinarello, C.A. Blood (1992) [Pubmed]
  28. Expression of type II nitric oxide synthase in primary human astrocytes and microglia: role of IL-1beta and IL-1 receptor antagonist. Liu, J., Zhao, M.L., Brosnan, C.F., Lee, S.C. J. Immunol. (1996) [Pubmed]
  29. Unopposed interleukin-1 is necessary for increased plasma cytokine and eicosanoid levels to develop in severe sepsis. Slotman, G.J., Quinn, J.V., Wry, P.C., Brathwaite, C.E., Friedman, B.M. Ann. Surg. (1997) [Pubmed]
  30. Human synovial fibroblasts coexpress IL-1 receptor type I and type II mRNA. The increased level of the IL-1 receptor in osteoarthritic cells is related to an increased level of the type I receptor. Sadouk, M.B., Pelletier, J.P., Tardif, G., Kiansa, K., Cloutier, J.M., Martel-Pelletier, J. Lab. Invest. (1995) [Pubmed]
  31. Muscle cytokine mRNA changes after 2.5 h of cycling: influence of carbohydrate. Nieman, D.C., Davis, J.M., Henson, D.A., Gross, S.J., Dumke, C.L., Utter, A.C., Vinci, D.M., Carson, J.A., Brown, A., McAnulty, S.R., McAnulty, L.S., Triplett, N.T. Medicine and science in sports and exercise. (2005) [Pubmed]
  32. Elaboration of interleukin 1-receptor antagonist is not attenuated by glucocorticoids after endotoxemia. Santos, A.A., Scheltinga, M.R., Lynch, E., Brown, E.F., Lawton, P., Chambers, E., Browning, J., Dinarello, C.A., Wolff, S.M., Wilmore, D.W. Archives of surgery (Chicago, Ill. : 1960) (1993) [Pubmed]
  33. Association of IL-1beta and IL-1 receptor antagonist haplotypes with rate of decline in lung function in smokers. Joos, L., McIntyre, L., Ruan, J., Connett, J.E., Anthonisen, N.R., Weir, T.D., Paré, P.D., Sandford, A.J. Thorax (2001) [Pubmed]
  34. Interleukin 1 autocrine growth system in human multiple myeloma. Nagata, K., Tanaka, Y., Oda, S., Yamashita, U., Eto, S. Jpn. J. Clin. Oncol. (1991) [Pubmed]
  35. The interleukin-1 receptor-associated kinase is degraded by proteasomes following its phosphorylation. Yamin, T.T., Miller, D.K. J. Biol. Chem. (1997) [Pubmed]
  36. The interleukin-1 receptor binds the human interleukin-1 alpha precursor but not the interleukin-1 beta precursor. Mosley, B., Urdal, D.L., Prickett, K.S., Larsen, A., Cosman, D., Conlon, P.J., Gillis, S., Dower, S.K. J. Biol. Chem. (1987) [Pubmed]
  37. Dysregulation of LPS-induced Toll-like receptor 4-MyD88 complex formation and IL-1 receptor-associated kinase 1 activation in endotoxin-tolerant cells. Medvedev, A.E., Lentschat, A., Wahl, L.M., Golenbock, D.T., Vogel, S.N. J. Immunol. (2002) [Pubmed]
  38. The interleukin 1 receptor: ligand interactions and signal transduction. Auron, P.E. Cytokine Growth Factor Rev. (1998) [Pubmed]
  39. Gastrin secretion from primary cultures of rabbit antral G cells: stimulation by inflammatory cytokines. Weigert, N., Schaffer, K., Schusdziarra, V., Classen, M., Schepp, W. Gastroenterology (1996) [Pubmed]
  40. X-ray structure of interleukin-1 receptor antagonist at 2.0-A resolution. Vigers, G.P., Caffes, P., Evans, R.J., Thompson, R.C., Eisenberg, S.P., Brandhuber, B.J. J. Biol. Chem. (1994) [Pubmed]
  41. Activation of p38 MAPK and/or JNK contributes to increased levels of VEGF secretion in human malignant glioma cells. Yoshino, Y., Aoyagi, M., Tamaki, M., Duan, L., Morimoto, T., Ohno, K. Int. J. Oncol. (2006) [Pubmed]
  42. TIRP, a novel Toll/interleukin-1 receptor (TIR) domain-containing adapter protein involved in TIR signaling. Bin, L.H., Xu, L.G., Shu, H.B. J. Biol. Chem. (2003) [Pubmed]
  43. Localization of interleukin-1 alpha, type 1 interleukin-1 receptor and interleukin-1 receptor antagonist in the synovial membrane and cartilage/pannus junction in rheumatoid arthritis. Deleuran, B.W., Chu, C.Q., Field, M., Brennan, F.M., Katsikis, P., Feldmann, M., Maini, R.N. Br. J. Rheumatol. (1992) [Pubmed]
  44. A gene expression restriction network mediated by sense and antisense Alu sequences located on protein-coding messenger RNAs. Liang, K.H., Yeh, C.T. BMC. Genomics. (2013) [Pubmed]
  45. Interleukin-1 beta induces interleukin-1 receptor antagonist and tumor necrosis factor binding protein in humans. Bargetzi, M.J., Lantz, M., Smith, C.G., Torti, F.M., Olsson, I., Eisenberg, S.P., Starnes, H.F. Cancer Res. (1993) [Pubmed]
  46. Plasma levels of cytokines in primary septic shock in humans: correlation with disease severity. Gårdlund, B., Sjölin, J., Nilsson, A., Roll, M., Wickerts, C.J., Wretlind, B. J. Infect. Dis. (1995) [Pubmed]
  47. Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants. O'Neill, L.A., Greene, C. J. Leukoc. Biol. (1998) [Pubmed]
  48. Stimulation and priming of human neutrophils by IL-1 alpha and IL-1 beta: complete inhibition by IL-1 receptor antagonist and no interaction with other cytokines. Yagisawa, M., Yuo, A., Kitagawa, S., Yazaki, Y., Togawa, A., Takaku, F. Exp. Hematol. (1995) [Pubmed]
  49. Elevated plasma levels of interleukin-1 receptor antagonist and interleukin-10 in patients with acute myocardial infarction. Shibata, M., Endo, S., Inada, K., Kuriki, S., Harada, M., Takino, T., Sato, N., Arakawa, N., Suzuki, T., Aoki, H., Suzuki, T., Hiramori, K. J. Interferon Cytokine Res. (1997) [Pubmed]
  50. Increased secretion of pro-inflammatory cytokines by circulating polymorphonuclear neutrophils and regulation by interleukin 10 during intestinal inflammation. Nikolaus, S., Bauditz, J., Gionchetti, P., Witt, C., Lochs, H., Schreiber, S. Gut (1998) [Pubmed]
  51. Autocrine interleukin-1 receptor antagonist can support malignant growth of glioblastoma by blocking growth-inhibiting autocrine loop of interleukin-1. Oelmann, E., Kraemer, A., Serve, H., Reufi, B., Oberberg, D., Patt, S., Herbst, H., Stein, H., Thiel, E., Berdel, W.E. Int. J. Cancer (1997) [Pubmed]
  52. Allelic variation at the interleukin-1 receptor antagonist gene is associated with early postmenopausal bone loss at the spine. Keen, R.W., Woodford-Richens, K.L., Lanchbury, J.S., Spector, T.D. Bone (1998) [Pubmed]
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