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Gene Review

Il1r1  -  interleukin 1 receptor, type I

Mus musculus

Synonyms: CD121 antigen-like family member A, CD121a, CD121b, IL-1 receptor alpha chain, IL-1R-1, ...
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Disease relevance of Il1r1


Psychiatry related information on Il1r1


High impact information on Il1r1

  • A VV open reading frame (ORF) that exhibits 30% amino acid identity to the type II IL-1 receptor was expressed in CV-1-EBNA cells and shown specifically to bind mIL-1 beta [9].
  • The product of the cloned complementary DNA binds both IL-1 alpha and IL-1 beta in a manner indistinguishable from that of the native T cell IL-1 receptor [10].
  • IL-1 receptor (IL-1R)/Toll-like receptor (TLR) family and TNF receptor (TNFR) superfamily members are critical for regulating multiple aspects of dendritic cell (DC) biology [11].
  • We show that the induction of antigen-specific ThIL-17 cells, but not T helper (Th)1 or Th2 cells, by immunization with antigens and adjuvants is abrogated in IL-1 receptor type I-deficient (IL-1RI(-/-)) mice [12].
  • The administration of a TLR-4 ligand, lipopolysaccharide, concomitant with arthritogenic serum in IL-1 receptor-deficient mice resulted in acute paw swelling, but not in MyD88-deficient mice [13].

Chemical compound and disease context of Il1r1

  • In acute dextran sulfate sodium-induced colitis, ICE-deficient (ICE KO) mice exhibited a greater than 50% decrease of the clinical scores weight loss, diarrhea, rectal bleeding, and colon length, whereas daily treatment with IL-1 receptor antagonist revealed a modest reduction in colitis severity [14].
  • Curcumin blocks interleukin-1 (IL-1) signaling by inhibiting the recruitment of the IL-1 receptor-associated kinase IRAK in murine thymoma EL-4 cells [15].
  • IL-1 receptor blockade quite significantly diminished lung tissue damage and granuloma formation, judging from morphometric index and lung hydroxyproline measurements [16].
  • Resistance to Pseudomonas aeruginosa Chronic Lung Infection Requires Cystic Fibrosis Transmembrane Conductance Regulator-Modulated Interleukin-1 (IL-1) Release and Signaling through the IL-1 Receptor [17].
  • To determine the relative in vivo importance of IL-1 release after allergen challenge to the subsequent endothelial adhesion and recruitment of eosinophils, the authors used ovalbumin sensitization and inhalation challenge to induce airway eosinophilia in IL-1 receptor type 1-deficient and control wild-type mice [18].

Biological context of Il1r1


Anatomical context of Il1r1

  • In contrast, tumorigenesis remained unaffected in either compound mutants of K19-C2mE containing Il1r1 or Rag2 mutation, indicating that neither interleukin-1beta signaling nor T cell/B cell response was required for the development of hyperplastic tumors [23].
  • At the highest dose (500 micrograms), significant decreases in osteoclast number occurred in mutant mice compared to wild-type mice: (i) a 64% reduction for the TNF p55(-/-)/IL-1R(-/-) mice, (ii) a 57% reduction for the IL-1R(-/-) mice, (iii) a 41% reduction for the TNF p55(-/-)/p75(-/-) mice, and (iv) a 38% reduction for the ICE(-/-) mice [24].
  • Influx of neutrophils was decreased in bronchoalveolar lavage fluids in IL-1R -/- mice compared with wild-type mice [25].
  • The absence of the IL-1 signal attenuated the outgrowth of Pseudomonas in lungs, as reflected by an increasing number of colony-forming units (cfu) during Pseudomonas pneumonia in wild-type mice and a concurrently decreasing number of cfu during pulmonary infection in IL-1R -/- mice (P < 0.05, IL-1R -/- mice vs. wild-type mice) [25].
  • Thus, IL-1R1 appears to be important for the recruitment of leukocytes across the blood-brain barrier [26].

Associations of Il1r1 with chemical compounds

  • In addition, anti-IL-1 receptor, type 1/p80 (IL-1R) antibodies were able to abrogate the response to nafenopin [27].
  • To assess the role of IL-1 receptor type I (IL-1RI) in the sickness-inducing effects of IL-1, IL-1beta and the cytokine inducer lipopolysaccharide were administered to IL-1RI-deficient mice (IL-1RI-/-) [28].
  • The increase at 2 h was confirmed by Northern blot analysis and was not prevented by latex occlusion performed immediately after tape-stripping mRNAs for the IL-1 (p80) receptor and TNF (p75) receptor were not detected in epidermis [29].
  • The analog also showed agonist activity as assayed by increased prostaglandin E2 synthesis from CHO cells expressing recombinant mouse IL-1 receptor [30].
  • Similar to IL-1, IL-6-mediated neuroprotection is also antagonized by pretreatment with IL-1 receptor antagonist and it is not affected by nicotine [31].

Physical interactions of Il1r1


Regulatory relationships of Il1r1

  • Thus, IL-1 alpha directly and indirectly stimulates the growth and differentiation of purified progenitors through the type I IL-1R but not the type II IL-1R [19].
  • Also, there may be a TLR2-specific, MyD88-independent IL-1 receptor/TLR-mediated pathway to activate NF-kappa B in the host defense against mycobacterial infection [34].
  • Neuroprotection provided by IL-1 is distinct from TNF-alpha because it is inhibited by IL-1 receptor antagonist; it is not antagonized by nicotine, but it is inhibited by a neutralizing Ab to nerve growth factor (NGF) [31].
  • Because IL-1 also stimulates the hypothalamic pituitary-adrenal axis resulting in the production of glucocorticoids (GC), we assessed whether in vivo treatment with HGF and glucocorticoids upregulates IL-1R [35].
  • Interleukin 4 (IL) 4 up-regulates gene and surface IL 1 receptor type I in murine T helper type 2 cells [36].

Other interactions of Il1r1


Analytical, diagnostic and therapeutic context of Il1r1


  1. Hepatocellular proliferation in response to a peroxisome proliferator does not require TNFalpha signaling. Anderson, S.P., Dunn, C.S., Cattley, R.C., Corton, J.C. Carcinogenesis (2001) [Pubmed]
  2. Tumor necrosis factor receptor 1-mediated signaling is required for skin cancer development induced by NF-kappaB inhibition. Lind, M.H., Rozell, B., Wallin, R.P., van Hogerlinden, M., Ljunggren, H.G., Toftgård, R., Sur, I. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  3. HSV-1-mediated IL-1 receptor antagonist gene therapy ameliorates MOG(35-55)-induced experimental autoimmune encephalomyelitis in C57BL/6 mice. Furlan, R., Bergami, A., Brambilla, E., Butti, E., De Simoni, M.G., Campagnoli, M., Marconi, P., Comi, G., Martino, G. Gene Ther. (2007) [Pubmed]
  4. The IL-1 receptor 1 is critical for Th2 cell type airway immune responses in a mild but not in a more severe asthma model. Schmitz, N., Kurrer, M., Kopf, M. Eur. J. Immunol. (2003) [Pubmed]
  5. MyD88 is a key mediator of anorexia, but not weight loss, induced by lipopolysaccharide and interleukin-1 beta. Ogimoto, K., Harris, M.K., Wisse, B.E. Endocrinology (2006) [Pubmed]
  6. The role of cytokines in the behavioral responses to endotoxin and influenza virus infection in mice: effects of acute and chronic administration of the interleukin-1-receptor antagonist (IL-1ra). Swiergiel, A.H., Smagin, G.N., Johnson, L.J., Dunn, A.J. Brain Res. (1997) [Pubmed]
  7. Interleukin-1 and host control of pulmonary histoplasmosis. Deepe, G.S., McGuinness, M. J. Infect. Dis. (2006) [Pubmed]
  8. Immunomorphological characteristics of animals with different levels of orientation and exploratory behavior. Markova, E.V., Chernova, T.G., Fillimonov, P.N., Korotkova, N.A., Abramov, V.V., Kozlov, V.A. Bull. Exp. Biol. Med. (2004) [Pubmed]
  9. Vaccinia and cowpox viruses encode a novel secreted interleukin-1-binding protein. Spriggs, M.K., Hruby, D.E., Maliszewski, C.R., Pickup, D.J., Sims, J.E., Buller, R.M., VanSlyke, J. Cell (1992) [Pubmed]
  10. cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily. Sims, J.E., March, C.J., Cosman, D., Widmer, M.B., MacDonald, H.R., McMahan, C.J., Grubin, C.E., Wignall, J.M., Jackson, J.L., Call, S.M. Science (1988) [Pubmed]
  11. TRAF6 is a critical factor for dendritic cell maturation and development. Kobayashi, T., Walsh, P.T., Walsh, M.C., Speirs, K.M., Chiffoleau, E., King, C.G., Hancock, W.W., Caamano, J.H., Hunter, C.A., Scott, P., Turka, L.A., Choi, Y. Immunity (2003) [Pubmed]
  12. A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. Sutton, C., Brereton, C., Keogh, B., Mills, K.H., Lavelle, E.C. J. Exp. Med. (2006) [Pubmed]
  13. Interleukin 1 receptor dependence of serum transferred arthritis can be circumvented by toll-like receptor 4 signaling. Choe, J.Y., Crain, B., Wu, S.R., Corr, M. J. Exp. Med. (2003) [Pubmed]
  14. IL-1 beta -converting enzyme (caspase-1) in intestinal inflammation. Siegmund, B., Lehr, H.A., Fantuzzi, G., Dinarello, C.A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  15. Curcumin blocks interleukin-1 (IL-1) signaling by inhibiting the recruitment of the IL-1 receptor-associated kinase IRAK in murine thymoma EL-4 cells. Jurrmann, N., Brigelius-Flohé, R., Böl, G.F. J. Nutr. (2005) [Pubmed]
  16. Interleukin-1 (IL-1) is an important cytokine in granulomatous alveolitis. Denis, M. Cell. Immunol. (1994) [Pubmed]
  17. Resistance to Pseudomonas aeruginosa Chronic Lung Infection Requires Cystic Fibrosis Transmembrane Conductance Regulator-Modulated Interleukin-1 (IL-1) Release and Signaling through the IL-1 Receptor. Reiniger, N., Lee, M.M., Coleman, F.T., Ray, C., Golan, D.E., Pier, G.B. Infect. Immun. (2007) [Pubmed]
  18. Inhibition of eosinophilic inflammation in allergen-challenged, IL-1 receptor type 1-deficient mice is associated with reduced eosinophil rolling and adhesion on vascular endothelium. Broide, D.H., Campbell, K., Gifford, T., Sriramarao, P. Blood (2000) [Pubmed]
  19. Interleukin-1 (IL-1) directly and indirectly promotes hematopoietic cell growth through type I IL-1 receptor. Hestdal, K., Ruscetti, F.W., Chizzonite, R., Ortiz, M., Gooya, J.M., Longo, D.L., Keller, J.R. Blood (1994) [Pubmed]
  20. Chromosomal location of murine and human IL-1 receptor genes. Copeland, N.G., Silan, C.M., Kingsley, D.M., Jenkins, N.A., Cannizzaro, L.A., Croce, C.M., Huebner, K., Sims, J.E. Genomics (1991) [Pubmed]
  21. Differential gene expression for IL-1 receptor antagonist, IL-1, and TNF receptors and IL-1 and TNF synthesis may explain IL-1-induced resistance to infection. Vogels, M.T., Mensink, E.J., Ye, K., Boerman, O.C., Verschueren, C.M., Dinarello, C.A., van der Meer, J.W. J. Immunol. (1994) [Pubmed]
  22. Early response cytokines and innate immunity: essential roles for TNF receptor 1 and type I IL-1 receptor during Escherichia coli pneumonia in mice. Mizgerd, J.P., Spieker, M.R., Doerschuk, C.M. J. Immunol. (2001) [Pubmed]
  23. Hyperplastic gastric tumors with spasmolytic polypeptide-expressing metaplasia caused by tumor necrosis factor-alpha-dependent inflammation in cyclooxygenase-2/microsomal prostaglandin E synthase-1 transgenic mice. Oshima, M., Oshima, H., Matsunaga, A., Taketo, M.M. Cancer Res. (2005) [Pubmed]
  24. Interleukin-1 and tumor necrosis factor activities partially account for calvarial bone resorption induced by local injection of lipopolysaccharide. Chiang, C.Y., Kyritsis, G., Graves, D.T., Amar, S. Infect. Immun. (1999) [Pubmed]
  25. Role of interleukin-1 in the pulmonary immune response during Pseudomonas aeruginosa pneumonia. Schultz, M.J., Rijneveld, A.W., Florquin, S., Edwards, C.K., Dinarello, C.A., van der Poll, T. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  26. IL-1 type I receptor plays a key role in mediating the recruitment of leukocytes into the central nervous system. Ching, S., He, L., Lai, W., Quan, N. Brain Behav. Immun. (2005) [Pubmed]
  27. Role for tumor necrosis factor alpha receptor 1 and interleukin-1 receptor in the suppression of mouse hepatocyte apoptosis by the peroxisome proliferator nafenopin. West, D.A., James, N.H., Cosulich, S.C., Holden, P.R., Brindle, R., Rolfe, M., Roberts, R.A. Hepatology (1999) [Pubmed]
  28. Role of interleukin-1beta and tumour necrosis factor-alpha in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice. Bluthé, R.M., Layé, S., Michaud, B., Combe, C., Dantzer, R., Parnet, P. Eur. J. Neurosci. (2000) [Pubmed]
  29. Barrier disruption increases gene expression of cytokines and the 55 kD TNF receptor in murine skin. Wood, L.C., Stalder, A.K., Liou, A., Campbell, I.L., Grunfeld, C., Elias, P.M., Feingold, K.R. Exp. Dermatol. (1997) [Pubmed]
  30. Conversion of the interleukin 1 receptor antagonist into an agonist by site-specific mutagenesis. Ju, G., Labriola-Tompkins, E., Campen, C.A., Benjamin, W.R., Karas, J., Plocinski, J., Biondi, D., Kaffka, K.L., Kilian, P.L., Eisenberg, S.P. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  31. Inflammatory cytokines IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha impart neuroprotection to an excitotoxin through distinct pathways. Carlson, N.G., Wieggel, W.A., Chen, J., Bacchi, A., Rogers, S.W., Gahring, L.C. J. Immunol. (1999) [Pubmed]
  32. Modulation of the nuclear factor kappa B pathway by Shp-2 tyrosine phosphatase in mediating the induction of interleukin (IL)-6 by IL-1 or tumor necrosis factor. You, M., Flick, L.M., Yu, D., Feng, G.S. J. Exp. Med. (2001) [Pubmed]
  33. IL-1beta epitope mapping using site-directed mutagenesis and hydrogen-deuterium exchange mass spectrometry analysis. Lu, J., Witcher, D.R., White, M.A., Wang, X., Huang, L., Rathnachalam, R., Beals, J.M., Kuhstoss, S. Biochemistry (2005) [Pubmed]
  34. Mycobacterial infection in MyD88-deficient mice. Sugawara, I., Yamada, H., Mizuno, S., Takeda, K., Akira, S. Microbiol. Immunol. (2003) [Pubmed]
  35. Hematopoietic growth factors and glucocorticoids synergize to mimic the effects of IL-1 on granulocyte differentiation and IL-1 receptor induction on bone marrow cells in vivo. Dubois, C.M., Neta, R., Keller, J.R., Jacobsen, S.E., Oppenheim, J.J., Ruscetti, F. Exp. Hematol. (1993) [Pubmed]
  36. Interleukin 4 (IL) 4 up-regulates gene and surface IL 1 receptor type I in murine T helper type 2 cells. Koch, K.C., Ye, K., Clark, B.D., Dinarello, C.A. Eur. J. Immunol. (1992) [Pubmed]
  37. Interleukin-6 is an afferent signal to the hypothalamo-pituitary-adrenal axis during local inflammation in mice. Turnbull, A.V., Prehar, S., Kennedy, A.R., Little, R.A., Hopkins, S.J. Endocrinology (2003) [Pubmed]
  38. Effects of 2-deoxy-D-glucose administration on cytokine production in BDF1 mice. Dréau, D., Morton, D.S., Foster, M., Fowler, N., Sonnenfeld, G. J. Interferon Cytokine Res. (2000) [Pubmed]
  39. Specific role of interleukin-1 in hepatic neutrophil recruitment after ischemia/reperfusion. Kato, A., Gabay, C., Okaya, T., Lentsch, A.B. Am. J. Pathol. (2002) [Pubmed]
  40. Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression. Layé, S., Gheusi, G., Cremona, S., Combe, C., Kelley, K., Dantzer, R., Parnet, P. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2000) [Pubmed]
  41. Understanding the dendritic cell lineage through a study of cytokine receptors. Kämpgen, E., Koch, F., Heufler, C., Eggert, A., Gill, L.L., Gillis, S., Dower, S.K., Romani, N., Schuler, G. J. Exp. Med. (1994) [Pubmed]
  42. Ligand-induced desensitization of interleukin 1 receptor-initiated intracellular signaling events in T helper lymphocytes. McKean, D.J., Huntoon, C., Bell, M. J. Exp. Med. (1994) [Pubmed]
  43. Two high-affinity interleukin 1 receptors represent separate gene products. Chizzonite, R., Truitt, T., Kilian, P.L., Stern, A.S., Nunes, P., Parker, K.P., Kaffka, K.L., Chua, A.O., Lugg, D.K., Gubler, U. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
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