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Gene Review

Il6ra  -  interleukin 6 receptor, alpha

Mus musculus

Synonyms: CD126, IL-6 receptor alpha chain, IL-6 receptor subunit alpha, IL-6R, IL-6R 1, ...
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Disease relevance of Il6ra


High impact information on Il6ra


Biological context of Il6ra


Anatomical context of Il6ra


Associations of Il6ra with chemical compounds

  • The function of IL-6R in the luminal and glandular epithelium might be different from that in the stroma during the implantation period [15].
  • There was no correlation between the signal strength of the IL-6R mRNA and the serum concentrations of progesterone and 17beta-estradiol, which show a monophasic rise in the non-pregnant sexual cycle [15].
  • We report that 17beta-estradiol or dihydrotestosterone in vitro decreased the abundance of the gp80 mRNA as well as the mRNA of the signal-transducing subunit of the IL-6 receptor (gp130) in cells of the bone marrow stromal/osteoblastic lineage, and also decreased gp130 protein levels [9].
  • These effects were suppressed by adding neutralizing antibodies against IL-1alpha or IL-6R and were totally abolished by adding nonsteroidal antiinflammatory drugs, such as indomethacin and a selective cyclooxygenase-2 (COX-2) inhibitor (NS398) [16].
  • Parallel analyses, using CD34(+)Lin(-) cells derived from murine ES cell cultures, showed no apparent expression of flt3, integrin alphaL, or IL-6 receptor, whereas corresponding cell preparations isolated from mouse BM expressed high levels of all of these genes [17].

Physical interactions of Il6ra

  • In contrast, the IL-6/IL-6R complexes have a higher inflammatory potential [18].

Regulatory relationships of Il6ra

  • Interleukin-6-induced IMCE cell proliferation was blocked by the addition of a neutralizing anti-IL-6R antibody [8].
  • In both strains, IL-6R was induced in CD4+ or CD8+ thymocytes after 2 days of culture, suggesting that CD4+ thymocytes in MRL/lpr have a potential to express IL-6R [19].

Other interactions of Il6ra

  • A soluble form of IL-6R (sIL-6R), which lacks transmembrane and cytoplasmic regions, retains the ability to bind IL-6 and signal through gp130 [20].
  • Cytokine stimulation of R1 and R2 cells induced cell cycle progression with elevated or induced expression of c-kit, c-fms, IL-2R, and IL-6R [21].
  • Antibodies neutralising interleukin (IL)-1alpha, IL-1beta, soluble IL-6 receptor, IL-17, or tumour necrosis factor-alpha, when added to individual SFs, only occasionally decreased the bone-resorbing activity [22].
  • The new receptor, named NR1, was most similar in sequence and predicted structure to the alpha-chain of the IL-6 receptor and mRNA was expressed in the 3T3-L1 pre-adipocytic cell line and in a range of primary tissues [23].
  • Expression of either dominant negative protein abolished osteoclast formation stimulated by IL-6 + soluble IL-6 receptor, oncostatin M, or IL-1 but not by parathyroid hormone or 1,25-dihydroxyvitamin D3 [24].

Analytical, diagnostic and therapeutic context of Il6ra

  • The increase in IL-6 and IL-6R was confirmed by western blotting using epidermal homogenates and was partially prevented by occlusion immediately after barrier disruption [11].
  • During the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs), IL-6R and gp130 expression in the mononuclear cells, stromal cells, and TRAP-positive MNCs were quantitated, using a laser cytometer with a fluorescence confocal microscopy [14].
  • The lung fibroblasts expressed IL-6 receptors on their surface as determined by flow cytometry using a rat anti-mouse IL-6 receptor antibody (15A7).(ABSTRACT TRUNCATED AT 250 WORDS)[25]
  • Thus, IL6-PE4E may be useful for ex vivo purging of IL-6R+ leukemic cells in an autologous bone marrow transplantation setting and possibly for therapy of residual, chemotherapy-resistant disease [26].
  • This reduction in bioactivity was shown to be due to a decreased capacity of the mutant protein to trigger IL-6 receptor-alpha-chain-dependent binding to the IL-6 signal transducer, gp130 [27].


  1. Prostaglandin E2 mediates growth arrest in NFS-60 cells by down-regulating interleukin-6 receptor expression. de Silva, K.I., Daud, A.N., Deng, J., Jones, S.B., Gamelli, R.L., Shankar, R. Biochem. J. (2003) [Pubmed]
  2. Inverse regulation of interleukin-6 (IL-6) and IL-6 receptor in histamine deficient histidine decarboxylase-knock-out mice. Horváth, B.V., Falus, A., Tóth, S., Szalai, C., Lázár-Molnár, E., Holub, M.C., Buzás, E., Nagy, A., Fulop, A.K. Immunol. Lett. (2002) [Pubmed]
  3. Unmasking by soluble IL-6 receptor of IL-6 effect on metastatic melanoma: growth inhibition and differentiation of B16-F10.9 tumor cells. Oh, J.W., Katz, A., Harroch, S., Eisenbach, L., Revel, M., Chebath, J. Oncogene (1997) [Pubmed]
  4. Interleukin-6 receptor blockage ameliorates murine lupus nephritis. Kiberd, B.A. J. Am. Soc. Nephrol. (1993) [Pubmed]
  5. Interleukin 6 (IL-6) and its receptor (IL-6R) in myeloma/plasmacytoma. Suematsu, S., Hibi, M., Sugita, T., Saito, M., Murakami, M., Matsusaka, T., Matsuda, T., Hirano, T., Taga, T., Kishimoto, T. Curr. Top. Microbiol. Immunol. (1990) [Pubmed]
  6. Activation-induced inhibition of interleukin 6-mediated T cell survival and signal transducer and activator of transcription 1 signaling. Teague, T.K., Schaefer, B.C., Hildeman, D., Bender, J., Mitchell, T., Kappler, J.W., Marrack, P. J. Exp. Med. (2000) [Pubmed]
  7. Accelerated Nerve Regeneration in Mice by upregulated expression of interleukin (IL) 6 and IL-6 receptor after trauma. Hirota, H., Kiyama, H., Kishimoto, T., Taga, T. J. Exp. Med. (1996) [Pubmed]
  8. Interleukin-6 production induced by leptin treatment promotes cell proliferation in an Apc (Min/+) colon epithelial cell line. Fenton, J.I., Hursting, S.D., Perkins, S.N., Hord, N.G. Carcinogenesis (2006) [Pubmed]
  9. Regulation of the gp80 and gp130 subunits of the IL-6 receptor by sex steroids in the murine bone marrow. Lin, S.C., Yamate, T., Taguchi, Y., Borba, V.Z., Girasole, G., O'Brien, C.A., Bellido, T., Abe, E., Manolagas, S.C. J. Clin. Invest. (1997) [Pubmed]
  10. Retinoic acid inhibits interleukin-6-induced macrophage differentiation and apoptosis in a murine hematopoietic cell line, Y6. Oritani, K., Kaisho, T., Nakajima, K., Hirano, T. Blood (1992) [Pubmed]
  11. The interleukin-6 cytokine system regulates epidermal permeability barrier homeostasis. Wang, X.P., Schunck, M., Kallen, K.J., Neumann, C., Trautwein, C., Rose-John, S., Proksch, E. J. Invest. Dermatol. (2004) [Pubmed]
  12. Differentiation and growth arrest signals are generated through the cytoplasmic region of gp130 that is essential for Stat3 activation. Yamanaka, Y., Nakajima, K., Fukada, T., Hibi, M., Hirano, T. EMBO J. (1996) [Pubmed]
  13. Interleukin-6, hepatocyte growth factor, and their receptors in biliary epithelial cells during a type I ductular reaction in mice: interactions between the periductal inflammatory and stromal cells and the biliary epithelium. Liu, Z., Sakamoto, T., Ezure, T., Yokomuro, S., Murase, N., Michalopoulos, G., Demetris, A.J. Hepatology (1998) [Pubmed]
  14. Expression of IL-6 receptor and GP130 in mouse bone marrow cells during osteoclast differentiation. Gao, Y., Morita, I., Maruo, N., Kubota, T., Murota, S., Aso, T. Bone (1998) [Pubmed]
  15. Localization of interleukin-6 receptor mRNA in the pregnant and non-pregnant mouse uterus. Hondo, E., Kokubu, K., Kato, K., Kiso, Y. J. Reprod. Dev. (2005) [Pubmed]
  16. Transcriptional induction of cyclooxygenase-2 in osteoblasts is involved in interleukin-6-induced osteoclast formation. Tai, H., Miyaura, C., Pilbeam, C.C., Tamura, T., Ohsugi, Y., Koishihara, Y., Kubodera, N., Kawaguchi, H., Raisz, L.G., Suda, T. Endocrinology (1997) [Pubmed]
  17. Comparative gene expression in hematopoietic progenitor cells derived from embryonic stem cells. Lu, S.J., Li, F., Vida, L., Honig, G.R. Exp. Hematol. (2002) [Pubmed]
  18. Pathogenic role of interleukin-6 in the development of sepsis. Part II: Significance of anti-interleukin-6 and anti-soluble interleukin-6 receptor-alpha antibodies in a standardized murine contact burn model. Pallua, N., Low, J.F., von Heimburg, D. Crit. Care Med. (2003) [Pubmed]
  19. Abnormal distribution of IL-6 receptor in aged MRL/lpr mice: elevated expression on B cells and absence on CD4+ cells. Kobayashi, I., Matsuda, T., Saito, T., Yasukawa, K., Kikutani, H., Hirano, T., Taga, T., Kishimoto, T. Int. Immunol. (1992) [Pubmed]
  20. Directly linked soluble IL-6 receptor-IL-6 fusion protein induces astrocyte differentiation from neuroepithelial cells via activation of STAT3. Takizawa, T., Yanagisawa, M., Ochiai, W., Yasukawa, K., Ishiguro, T., Nakashima, K., Taga, T. Cytokine (2001) [Pubmed]
  21. Cytokine receptor repertoire and cytokine responsiveness of Ho(dull)/Rh(dull) stem cells with differing potentials for G1/S phase progression. Reddy, G.P., McAuliffe, C.I., Pang, L., Quesenberry, P.J., Bertoncello, I. Exp. Hematol. (2002) [Pubmed]
  22. Effects on osteoclast and osteoblast activities in cultured mouse calvarial bones by synovial fluids from patients with a loose joint prosthesis and from osteoarthritis patients. Andersson, M.K., Lundberg, P., Ohlin, A., Perry, M.J., Lie, A., Stark, A., Lerner, U.H. Arthritis Res. Ther. (2007) [Pubmed]
  23. Cloning of a murine IL-11 receptor alpha-chain; requirement for gp130 for high affinity binding and signal transduction. Hilton, D.J., Hilton, A.A., Raicevic, A., Rakar, S., Harrison-Smith, M., Gough, N.M., Begley, C.G., Metcalf, D., Nicola, N.A., Willson, T.A. EMBO J. (1994) [Pubmed]
  24. STAT3 activation in stromal/osteoblastic cells is required for induction of the receptor activator of NF-kappaB ligand and stimulation of osteoclastogenesis by gp130-utilizing cytokines or interleukin-1 but not 1,25-dihydroxyvitamin D3 or parathyroid hormone. O'Brien, C.A., Gubrij, I., Lin, S.C., Saylors, R.L., Manolagas, S.C. J. Biol. Chem. (1999) [Pubmed]
  25. Interleukin-6 is an autocrine growth factor for murine lung fibroblast subsets. Fries, K.M., Felch, M.E., Phipps, R.P. Am. J. Respir. Cell Mol. Biol. (1994) [Pubmed]
  26. Expression of interleukin-6 receptors by pediatric acute lymphoblastic leukemia cells with the t(4;11) translocation: a possible target for therapy with recombinant IL6-Pseudomonas exotoxin. Gu, L., Zhou, M., Jurickova, I., Yeager, A.M., Kreitman, R.J., Phillips, C.N., Findley, H.W. Leukemia (1997) [Pubmed]
  27. Leucine-58 in the putative 5th helical region of human interleukin (IL)-6 is important for activation of the IL-6 signal transducer, gp130. de Hon, F.D., Klaasse Bos, H.K., Ebeling, S.B., Grötzinger, J., Kurapkat, G., Rose-John, S., Aarden, L.A., Brakenhoff, J.P. FEBS Lett. (1995) [Pubmed]
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