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Gene Review

IL6R  -  interleukin 6 receptor

Homo sapiens

Synonyms: CD126, IL-6 receptor subunit alpha, IL-6R 1, IL-6R subunit alpha, IL-6R-1, ...
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Disease relevance of IL6R

  • An Asp358Ala polymorphism of the IL6R has been reported to associate with obesity in Pima Indians [1].
  • METHODS: The activation of IL6, IL6R and gp130 messenger ribonucleic acid (mRNA) and protein was studied via reverse transcription-polymerase chain reaction (RT-PCR) and immunohistology in donor hearts (n = 6) and compared with patients undergoing evaluation of ventricular arrhythmias (control, n = 9) or with advanced heart failure (n = 20) [2].
  • We studied the role of gp80 in binding, internalization and down-regulation of the hepatic IL6-receptor (IL6R) by its ligand in human hepatoma cells (HepG2) [3].
  • IL6R expression could be further demonstrated in all LCLs analysed, in five out of seven EBV positive BLs and two out of three B95-8 convertants, but only in one out of the six EBV negative BL cell lines [4].
  • The human interleukin-6 receptor (IL6R) is responsible for signal transduction of IL6 that might have associations with immune diseases and various infectious diseases [5].
  • Production of sIL-6R by autoreactive CD4 T cells may contribute to their role in the development of autoimmune disease by conferring IL-6-responsiveness to cells lacking IL-6R such as synoviocytes [6].

Psychiatry related information on IL6R


High impact information on IL6R


Chemical compound and disease context of IL6R


Biological context of IL6R

  • The IL6R gene maps to an important candidate locus for type 2 diabetes on chromosome 1q21 [1].
  • The down-regulation of the hepatic IL6R by its ligand might play an important role as a protection against overstimulation [3].
  • We identified six single nucleotide polymorphisms (SNPs) in the IL6R gene: a predicted Asp --> Ala substitution at position 358, a variant in the 3'-untranslated region, and 4 intronic SNPs [19].
  • We sequenced 6kb of the IL6R gene, corresponding to all exons, exon-intron boundaries, and 2kb of promoter in 30 Pima Indians [19].
  • Association between IL6R genotype and BMI (kg/m(2)) was assessed in approximately 700 nondiabetic, full-heritage Pima Indians [19].

Anatomical context of IL6R

  • Right ventricles of failing hearts showed IL6, IL6R and gp130 mRNA levels comparable with those found in donor hearts [2].
  • This localization confirms and extends the provisional assignment of the IL6R alpha gene to chromosome 1, for which a panel of somatic cell hybrids was used [20].
  • Similar oscillations in the number of white blood cells, IL6R+ cells, CD34+ cells and colony-forming unit-granulocyte/macrophage (CFU-GM) in PB could be observed and the peak expression of mRNA was compatible with the expression of antigen [21].
  • On the other hand, neither sIgM+ nor sIgG+ B cells from appendix express IL6R [22].
  • Scatchard analysis of (125I)-IL-6 binding data showed the presence of high (Kd, 3 x 10(-10) M) and low (Kd, 6 x 10(-8) M) affinity IL6R on both lymphocyte populations [23].

Associations of IL6R with chemical compounds


Physical interactions of IL6R

  • We studied the capacity of these mutants to form an IL-6/IL-6R complex and their ability to transduce the signal [28].
  • The soluble form of IL-6R (sIL-6R) can bind its ligand and induce cellular responses by association with gp130, thus acting as an IL-6 agonist [29].
  • These results suggest that the IL-11 binding component is different from the gp80/IL-6 receptor [30].
  • Furthermore, cholangiocytes possessed the IL-6 receptor complex subunits and intact signaling mechanisms leading to activation of signal transducers and activators of transcription (STAT) factors [31].

Enzymatic interactions of IL6R


Regulatory relationships of IL6R


Other interactions of IL6R


Analytical, diagnostic and therapeutic context of IL6R


  1. Variation in the interleukin-6 receptor gene associates with type 2 diabetes in Danish whites. Hamid, Y.H., Urhammer, S.A., Jensen, D.P., Glümer, C., Borch-Johnsen, K., Jørgensen, T., Hansen, T., Pedersen, O. Diabetes (2004) [Pubmed]
  2. The interleukin-6/interleukin-6-receptor system is activated in donor hearts. Plenz, G., Eschert, H., Erren, M., Wichter, T., Böhm, M., Flesch, M., Scheld, H.H., Deng, M.C. J. Am. Coll. Cardiol. (2002) [Pubmed]
  3. The hepatic interleukin-6 receptor. Down-regulation of the interleukin-6 binding subunit (gp80) by its ligand. Zohlnhöfer, D., Graeve, L., Rose-John, S., Schooltink, H., Dittrich, E., Heinrich, P.C. FEBS Lett. (1992) [Pubmed]
  4. IL6 and IL6 receptor expression in Burkitt's lymphoma and lymphoblastoid cell lines: promotion of IL6 receptor expression by EBV. Klein, S.C., Jücker, M., Abts, H., Tesch, H. Hematological oncology. (1995) [Pubmed]
  5. Identification of novel SNPs in the interleukin 6 receptor gene (IL6R). Kim, L.H., Lee, H.S., Kim, Y.J., Jung, J.H., Kim, J.Y., Park, B.L., Shin, H.D. Hum. Mutat. (2003) [Pubmed]
  6. Cutting edge: soluble IL-6R is produced by IL-6R ectodomain shedding in activated CD4 T cells. Briso, E.M., Dienz, O., Rincon, M. J. Immunol. (2008) [Pubmed]
  7. Polymorphisms of the gene encoding the inflammatory cytokine interleukin-6 determine the magnitude of the increase in soluble interleukin-6 receptor levels in Alzheimer's disease. Results of a pilot study. Bagli, M., Papassotiropoulos, A., Hampel, H., Becker, K., Jessen, F., Bürger, K., Ptok, U., Rao, M.L., Möller, H.J., Maier, W., Heun, R. European archives of psychiatry and clinical neuroscience. (2003) [Pubmed]
  8. Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events. Maes, M., Lin, A.H., Delmeire, L., Van Gastel, A., Kenis, G., De Jongh, R., Bosmans, E. Biol. Psychiatry (1999) [Pubmed]
  9. T-lymphocyte interleukin 6 receptor binding in patients with dementia of Alzheimer type. Bongioanni, P., Boccardi, B., Borgna, M., Rossi, B. Arch. Neurol. (1998) [Pubmed]
  10. Linkage of pycnodysostosis to chromosome 1q21 by homozygosity mapping. Gelb, B.D., Edelson, J.G., Desnick, R.J. Nat. Genet. (1995) [Pubmed]
  11. Homology of the p40 subunit of natural killer cell stimulatory factor (NKSF) with the extracellular domain of the interleukin-6 receptor. Gearing, D.P., Cosman, D. Cell (1991) [Pubmed]
  12. Molecular cloning and expression of an IL-6 signal transducer, gp130. Hibi, M., Murakami, M., Saito, M., Hirano, T., Taga, T., Kishimoto, T. Cell (1990) [Pubmed]
  13. Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in crohn disease and experimental colitis in vivo. Atreya, R., Mudter, J., Finotto, S., Müllberg, J., Jostock, T., Wirtz, S., Schütz, M., Bartsch, B., Holtmann, M., Becker, C., Strand, D., Czaja, J., Schlaak, J.F., Lehr, H.A., Autschbach, F., Schürmann, G., Nishimoto, N., Yoshizaki, K., Ito, H., Kishimoto, T., Galle, P.R., Rose-John, S., Neurath, M.F. Nat. Med. (2000) [Pubmed]
  14. Glucocorticoid up-regulation of high-affinity interleukin 6 receptors on human epithelial cells. Snyers, L., De Wit, L., Content, J. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  15. Interleukin-1 (IL-1)-induced IL-6- and IL-6-receptor-mediated release of human chorionic gonadotropin by choriocarcinoma cell lines (Jar and HCCM-5) activates adenosine 3',5'-monophosphate-independent signal transduction pathway. Taniguchi, T., Matsuzaki, N., Jo, T., Saji, F., Taga, T., Hirano, T., Kishimoto, T., Tanizawa, O. J. Clin. Endocrinol. Metab. (1992) [Pubmed]
  16. Signal Transduction by Human Herpesvirus 8 Viral Interleukin-6 (vIL-6) Is Modulated by the Nonsignaling gp80 Subunit of the IL-6 Receptor Complex and Is Distinct from Signaling Induced by Human IL-6. Hu, F., Nicholas, J. J. Virol. (2006) [Pubmed]
  17. Proteolysis of interleukin-6 receptor (IL-6R) by Porphyromonas gingivalis cysteine proteinases (gingipains) inhibits interleukin-6-mediated cell activation. Oleksy, A., Banbula, A., Bugno, M., Travis, J., Potempa, J. Microb. Pathog. (2002) [Pubmed]
  18. Suramin interferes with interleukin-6 receptor binding in vitro and inhibits colon-26-mediated experimental cancer cachexia in vivo. Strassmann, G., Fong, M., Freter, C.E., Windsor, S., D'Alessandro, F., Nordan, R.P. J. Clin. Invest. (1993) [Pubmed]
  19. Variants in the interleukin 6 receptor gene are associated with obesity in Pima Indians. Wolford, J.K., Colligan, P.B., Gruber, J.D., Bogardus, C. Mol. Genet. Metab. (2003) [Pubmed]
  20. The human interleukin-6 receptor alpha chain gene is localized on chromosome 1 band q21. Kluck, P.M., Wiegant, J., Jansen, R.P., Bolk, M.W., Raap, A.K., Willemze, R., Landegent, J.E. Hum. Genet. (1993) [Pubmed]
  21. Serum soluble IL-6 receptor levels during the mobilization of stem cells to peripheral blood. Omura, H., Kawatani, T., Tajima, F., Ishiga, K., Ohmura, H., Kawasaki, H., Nanba, E. Leuk. Lymphoma (2002) [Pubmed]
  22. Effects of IL6 on B cells in mucosal immune response and inflammation. Fujihashi, K., Kono, Y., Kiyono, H. Res. Immunol. (1992) [Pubmed]
  23. IL-6/BSF-2 selectively stimulates the GO----S progression of CD8+ lymphocytes. Bulgarini, D., Scalzo, S., Boccoli, G., Petrini, M., Quaranta, M.T., Camagna, A., Isacchi, G., Testa, U., Peschle, C. J. Biol. Regul. Homeost. Agents (1991) [Pubmed]
  24. Inhibitory effect of all-trans retinoic acid on the growth of freshly isolated myeloma cells via interference with interleukin-6 signal transduction. Ogata, A., Nishimoto, N., Shima, Y., Yoshizaki, K., Kishimoto, T. Blood (1994) [Pubmed]
  25. Myeloma cell growth arrest, apoptosis, and interleukin-6 receptor modulation induced by EB1089, a vitamin D3 derivative, alone or in association with dexamethasone. Puthier, D., Bataille, R., Barillé, S., Mellerin, M.P., Harousseau, J.L., Ponzio, A., Robillard, N., Wijdenes, J., Amiot, M. Blood (1996) [Pubmed]
  26. Shedding of the interleukin-6 (IL-6) receptor (gp80) determines the ability of IL-6 to induce gp130 phosphorylation in human osteoblasts. Vermes, C., Jacobs, J.J., Zhang, J., Firneisz, G., Roebuck, K.A., Glant, T.T. J. Biol. Chem. (2002) [Pubmed]
  27. Cellular cholesterol depletion triggers shedding of the human interleukin-6 receptor by ADAM10 and ADAM17 (TACE). Matthews, V., Schuster, B., Schütze, S., Bussmeyer, I., Ludwig, A., Hundhausen, C., Sadowski, T., Saftig, P., Hartmann, D., Kallen, K.J., Rose-John, S. J. Biol. Chem. (2003) [Pubmed]
  28. Analysis of the human interleukin-6/human interleukin-6 receptor binding interface at the amino acid level: proposed mechanism of interaction. Kalai, M., Montero-Julian, F.A., Grötzinger, J., Fontaine, V., Vandenbussche, P., Deschuyteneer, R., Wollmer, A., Brailly, H., Content, J. Blood (1997) [Pubmed]
  29. Soluble interleukin-6 receptor strongly increases the production of acute-phase protein by hepatoma cells but exerts minimal changes on human primary hepatocytes. Gabay, C., Silacci, P., Genin, B., Mentha, G., Le Coultre, C., Guerne, P.A. Eur. J. Immunol. (1995) [Pubmed]
  30. Involvement of gp130/interleukin-6 receptor transducing component in interleukin-11 receptor. Fourcin, M., Chevalier, S., Lebrun, J.J., Kelly, P., Pouplard, A., Wijdenes, J., Gascan, H. Eur. J. Immunol. (1994) [Pubmed]
  31. Lipopolysaccharide induces cholangiocyte proliferation via an interleukin-6-mediated activation of p44/p42 mitogen-activated protein kinase. Park, J., Gores, G.J., Patel, T. Hepatology (1999) [Pubmed]
  32. Selective proteolytic cleavage of IL-2 receptor and IL-6 receptor ligand binding chains by neutrophil-derived serine proteases at foci of inflammation. Bank, U., Reinhold, D., Schneemilch, C., Kunz, D., Synowitz, H.J., Ansorge, S. J. Interferon Cytokine Res. (1999) [Pubmed]
  33. Loss of IL-6 receptor expression in cervical carcinoma cells inhibits autocrine IL-6 stimulation: abrogation of constitutive monocyte chemoattractant protein-1 production. Hess, S., Smola, H., Sandaradura De Silva, U., Hadaschik, D., Kube, D., Baldus, S.E., Flucke, U., Pfister, H. J. Immunol. (2000) [Pubmed]
  34. A Kaposi's sarcoma-associated herpesvirus-encoded cytokine homolog (vIL-6) activates signaling through the shared gp130 receptor subunit. Molden, J., Chang, Y., You, Y., Moore, P.S., Goldsmith, M.A. J. Biol. Chem. (1997) [Pubmed]
  35. Soluble interleukin-6 receptor enhanced by oncostatin M induces major changes in gene expression profile of human hepatoma cells. Holub, M.C., Hegyesi, H., Igaz, P., Polgár, A., Toth, S., Falus, A. Immunol. Lett. (2002) [Pubmed]
  36. Expression of the interleukin 6 receptor in primary renal cell carcinoma. Costes, V., Liautard, J., Picot, M.C., Robert, M., Lequeux, N., Brochier, J., Baldet, P., Rossi, J.F. J. Clin. Pathol. (1997) [Pubmed]
  37. Interleukin-6 receptor antagonists inhibit interleukin-11 biological activity. Sun, R.X., Gennaro, C., Rocco, S., Gu, Z.J., Klein, B. Eur. Cytokine Netw. (1997) [Pubmed]
  38. IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. Murakami, M., Hibi, M., Nakagawa, N., Nakagawa, T., Yasukawa, K., Yamanishi, K., Taga, T., Kishimoto, T. Science (1993) [Pubmed]
  39. Disruption by interferon-alpha of an autocrine interleukin-6 growth loop in IL-6-dependent U266 myeloma cells by homologous and heterologous down-regulation of the IL-6 receptor alpha- and beta-chains. Schwabe, M., Brini, A.T., Bosco, M.C., Rubboli, F., Egawa, M., Zhao, J., Princler, G.L., Kung, H.F. J. Clin. Invest. (1994) [Pubmed]
  40. Expression of cytokine genes, cytokine receptor genes, and transcription factors in cultured Hodgkin and Reed-Sternberg cells. Gruss, H.J., Brach, M.A., Drexler, H.G., Bonifer, R., Mertelsmann, R.H., Herrmann, F. Cancer Res. (1992) [Pubmed]
  41. Relationship between circulating serum soluble interleukin-6 receptor and the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in multiple myeloma. Alexandrakis, M.G., Passam, F.H., Boula, A., Christophoridou, A., Aloizos, G., Roussou, P., Kyriakou, D.S. Ann. Hematol. (2003) [Pubmed]
  42. Combined interleukin 6 and soluble interleukin 6 receptor accelerates murine liver regeneration. Peters, M., Blinn, G., Jostock, T., Schirmacher, P., Meyer zum Büschenfelde, K.H., Galle, P.R., Rose-John, S. Gastroenterology (2000) [Pubmed]
  43. Hyperstimulation with interleukin 6 inhibits cell cycle progression after hepatectomy in mice. Wüstefeld, T., Rakemann, T., Kubicka, S., Manns, M.P., Trautwein, C. Hepatology (2000) [Pubmed]
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