IL-6R

Summary

Gene Symbol: IL-6R
Description: interleukin 6 receptor
Alias: CD126, IL-6R-1, IL-6RA, IL6Q, IL6RA, IL6RQ, gp80, interleukin-6 receptor subunit alpha, CD126 antigen, IL-6 receptor subunit alpha, IL-6R 1, membrane glycoprotein 80
Species: human
Products:     IL-6R

Top Publications

  1. Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, et al. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell. 1989;58:573-81 pubmed
    ..These findings indicate that the complex of IL-6 and IL-6-R can interact with a non-ligand-binding membrane glycoprotein, gp130, extracellularly and can provide the IL-6 signal. ..
  2. Briso E, Dienz O, Rincon M. Cutting edge: soluble IL-6R is produced by IL-6R ectodomain shedding in activated CD4 T cells. J Immunol. 2008;180:7102-6 pubmed
    ..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. ..
  3. Bustamante M, Nogues X, Mellibovsky L, Agueda L, Jurado S, Caceres E, et al. Polymorphisms in the interleukin-6 receptor gene are associated with bone mineral density and body mass index in Spanish postmenopausal women. Eur J Endocrinol. 2007;157:677-84 pubmed
    ..The IL6R gene may belong to the growing list of genes known to be involved in both phenotypes. ..
  4. Nishimoto N, Terao K, Mima T, Nakahara H, Takagi N, Kakehi T. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood. 2008;112:3959-64 pubmed publisher
    ..We also concluded that the increased level of free IL-6 during tocilizumab treatment closely reflects the actual endogenous IL-6 production and true disease activity. ..
  5. Rafiq S, Frayling T, Murray A, Hurst A, Stevens K, Weedon M, et al. A common variant of the interleukin 6 receptor (IL-6r) gene increases IL-6r and IL-6 levels, without other inflammatory effects. Genes Immun. 2007;8:552-9 pubmed
    ..A common variant of the IL-6r gene results in major changes in IL-6r and IL-6 serum levels, but with no apparent effect on gp130 levels or on inflammatory status in the general population. ..
  6. Schnabel R, Kerr K, Lubitz S, Alkylbekova E, Marcus G, Sinner M, et al. Large-scale candidate gene analysis in whites and African Americans identifies IL6R polymorphism in relation to atrial fibrillation: the National Heart, Lung, and Blood Institute's Candidate Gene Association Resource (CARe) project. Circ Cardiovasc Genet. 2011;4:557-64 pubmed publisher
    ..Additionally, we demonstrated that the chromosome 4 locus known from recent genome-wide association studies in whites is associated with AF in African Americans. ..
  7. Chalaris A, Gewiese J, Paliga K, Fleig L, Schneede A, Krieger K, et al. ADAM17-mediated shedding of the IL6R induces cleavage of the membrane stub by gamma-secretase. Biochim Biophys Acta. 2010;1803:234-45 pubmed publisher
    ..We therefore hypothesize that a potential IL6R intracellular domain fragment is not involved in nuclear signaling but rapidly degraded. ..
  8. Danik J, Pare G, Chasman D, Zee R, Kwiatkowski D, Parker A, et al. Novel loci, including those related to Crohn disease, psoriasis, and inflammation, identified in a genome-wide association study of fibrinogen in 17 686 women: the Women's Genome Health Study. Circ Cardiovasc Genet. 2009;2:134-41 pubmed publisher
  9. Jiang C, Lam T, Liu B, Lin J, Yue X, Jin Y, et al. Interleukin-6 receptor gene polymorphism modulates interleukin-6 levels and the metabolic syndrome: GBCS-CVD. Obesity (Silver Spring). 2010;18:1969-74 pubmed publisher
    ..023. These data, which are in accord with studies from white populations suggest the IL-6R SNP may play a role in the pathogenesis of the MES possibly through modulating IL-6 levels. ..

More Information

Publications77

  1. Dema B, Martínez A, Fernández Arquero M, Maluenda C, Polanco I, Figueredo M, et al. The IL6-174G/C polymorphism is associated with celiac disease susceptibility in girls. Hum Immunol. 2009;70:191-4 pubmed
    ..03-1.66; and vs controls: p = 0.003, OR = 1.30, 95% CI 1.09-1.55). The functional -174G/C IL6 polymorphism seems to influence CD susceptibility in girls. The gender-specific role of IL-6 in this pathology must be further investigated. ..
  2. Menon R, Velez D, Simhan H, Ryckman K, Jiang L, Thorsen P, et al. Multilocus interactions at maternal tumor necrosis factor-alpha, tumor necrosis factor receptors, interleukin-6 and interleukin-6 receptor genes predict spontaneous preterm labor in European-American women. Am J Obstet Gynecol. 2006;194:1616-24 pubmed
  3. Esteve E, Villuendas G, Mallolas J, Vendrell J, Lopez Bermejo A, Rodríguez M, et al. Polymorphisms in the interleukin-6 receptor gene are associated with body mass index and with characteristics of the metabolic syndrome. Clin Endocrinol (Oxf). 2006;65:88-91 pubmed
    ..The Asp358Ala and CA-repeat polymorphisms in the IL-6R gene are associated with obesity and characteristics of the metabolic syndrome in our population of Mediterranean subjects. ..
  4. Kanazawa T, Nishino H, Hasegawa M, Ohta Y, Iino Y, Ichimura K, et al. Interleukin-6 directly influences proliferation and invasion potential of head and neck cancer cells. Eur Arch Otorhinolaryngol. 2007;264:815-21 pubmed
    ..These results suggest that IL-6 can directly influence cell proliferation and the invasion potential as the first step of tumor metastasis. ..
  5. Velez D, Menon R, Thorsen P, Jiang L, Simhan H, Morgan N, et al. Ethnic differences in interleukin 6 (IL-6) and IL6 receptor genes in spontaneous preterm birth and effects on amniotic fluid protein levels. Ann Hum Genet. 2007;71:586-600 pubmed
    ..Our data support differential genetic control of levels of IL-6 in amniotic fluid between EA and AA. ..
  6. Egler R, Burlingame S, Nuchtern J, Russell H. Interleukin-6 and soluble interleukin-6 receptor levels as markers of disease extent and prognosis in neuroblastoma. Clin Cancer Res. 2008;14:7028-34 pubmed publisher
    ..Decreased PB sIL-6R levels correlated with the presence of metastatic disease. Further study of these markers in children with neuroblastoma seems warranted. ..
  7. Qi L, Rifai N, Hu F. Interleukin-6 receptor gene, plasma C-reactive protein, and diabetes risk in women. Diabetes. 2009;58:275-8 pubmed publisher
    ..21 (1.18-4.12), 3.77 (1.87-7.57), and 5.02 (2.4-10.5) in the noncarriers. IL6R variants were significantly associated with plasma CRP, independent of IL-6 levels. IL6R variants may interact with CRP in predicting diabetes risk. ..
  8. Velez D, Fortunato S, Williams S, Menon R. Interleukin-6 (IL-6) and receptor (IL6-R) gene haplotypes associate with amniotic fluid protein concentrations in preterm birth. Hum Mol Genet. 2008;17:1619-30 pubmed publisher
    ..In conclusion, our results suggest that IL-6 AF concentration, in situations of PTB, result from variation in IL-6 and more importantly IL-6R. ..
  9. Elliott P, Chambers J, Zhang W, Clarke R, Hopewell J, Peden J, et al. Genetic Loci associated with C-reactive protein levels and risk of coronary heart disease. JAMA. 2009;302:37-48 pubmed publisher
    ..The lack of concordance between the effect on coronary heart disease risk of CRP genotypes and CRP levels argues against a causal association of CRP with coronary heart disease. ..
  10. Hamid Y, Urhammer S, Jensen D, Glümer C, Borch Johnsen K, Jørgensen T, et al. Variation in the interleukin-6 receptor gene associates with type 2 diabetes in Danish whites. Diabetes. 2004;53:3342-5 pubmed
    ..In conclusion, the Asp358Ala polymorphism of the IL6R associates with type 2 diabetes in Danish whites. ..
  11. Santer F, Malinowska K, Culig Z, Cavarretta I. Interleukin-6 trans-signalling differentially regulates proliferation, migration, adhesion and maspin expression in human prostate cancer cells. Endocr Relat Cancer. 2010;17:241-53 pubmed publisher
    ..Collectively, these data suggest that selective targeting of IL-6TS might allow to refine the currently available experimental anti-IL-6 therapies against PC. ..
  12. Matthews V, Schuster B, Schütze S, Bussmeyer I, Ludwig A, Hundhausen C, et al. Cellular cholesterol depletion triggers shedding of the human interleukin-6 receptor by ADAM10 and ADAM17 (TACE). J Biol Chem. 2003;278:38829-39 pubmed
    ..For decades, high cholesterol levels have been considered harmful. This study indicates that low cholesterol levels may play a role in shedding of the membrane-bound IL-6R and thereby in the immunopathogenesis of human diseases. ..
  13. Okugawa Y, Miki C, Toiyama Y, Yasuda H, Yokoe T, Saigusa S, et al. Loss of tumoral expression of soluble IL-6 receptor is associated with disease progression in colorectal cancer. Br J Cancer. 2010;103:787-95 pubmed publisher
    ..In addition, tumoral IL-1beta expression was significantly correlated with sIL-6R expression. Loss of tumour expression of sIL-6R is associated with colorectal cancer disease progression. ..
  14. Dehghan A, Dupuis J, Barbalic M, Bis J, Eiriksdottir G, Lu C, et al. Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels. Circulation. 2011;123:731-8 pubmed publisher
    ..We identified 18 loci that were associated with CRP levels. Our study highlights immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation. ..
  15. Ferreira R, Freitag D, Cutler A, Howson J, Rainbow D, Smyth D, et al. Functional IL6R 358Ala allele impairs classical IL-6 receptor signaling and influences risk of diverse inflammatory diseases. PLoS Genet. 2013;9:e1003444 pubmed publisher
  16. Revez J, Bain L, Chapman B, Powell J, Jansen R, Duffy D, et al. A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk. Genes Immun. 2013;14:441-6 pubmed publisher
    ..04-fold (P=0.0419). Genetic risk scores based on IL6R regulatory variants may prove useful in explaining variation in clinical response to tocilizumab, an anti-IL-6R monoclonal antibody. ..
  17. Lagmay J, London W, Gross T, Termuhlen A, Sullivan N, Axel A, et al. Prognostic significance of interleukin-6 single nucleotide polymorphism genotypes in neuroblastoma: rs1800795 (promoter) and rs8192284 (receptor). Clin Cancer Res. 2009;15:5234-9 pubmed publisher
    ..Because the rs1800795 SNP [-174 IL-6 (G > C)] has been shown to correlate with production of IL-6, this cytokine may represent a target for development of new therapies in neuroblastoma. ..
  18. Colomiere M, Ward A, Riley C, Trenerry M, Cameron Smith D, Findlay J, et al. Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial-mesenchymal transition in ovarian carcinomas. Br J Cancer. 2009;100:134-44 pubmed publisher
    ..Such activation of STAT3 suggests a rationale for a combination of anti-STAT3 and EGFR/IL-6R therapy to suppress the peritoneal spread of ovarian cancer. ..
  19. Wang M, Song H, Jia J. Interleukin-6 receptor gene polymorphisms were associated with sporadic Alzheimer's disease in Chinese Han. Brain Res. 2010;1327:1-5 pubmed publisher
    ..None of the associations appeared to be modified by APOE epsilon4. We conclude that the -530T allele located in a putative regulatory region and the +48867C allele at the splice site may elevate the risk of SAD among the Han Chinese. ..
  20. Stephens O, Zhang Q, Qu P, Zhou Y, Chavan S, Tian E, et al. An intermediate-risk multiple myeloma subgroup is defined by sIL-6r: levels synergistically increase with incidence of SNP rs2228145 and 1q21 amplification. Blood. 2012;119:503-12 pubmed publisher
  21. Chen Z, Qian Q, Tang C, Ding J, Feng Y, Ma G. Association of two variants in the interleukin-6 receptor gene and premature coronary heart disease in a Chinese Han population. Mol Biol Rep. 2013;40:1021-6 pubmed publisher
    ..Further studies are warranted to elucidate the role of these two SNPs in the development of atherosclerosis and CHD. ..
  22. Gu F, Qureshi A, Niu T, Kraft P, Guo Q, Hunter D, et al. Interleukin and interleukin receptor gene polymorphisms and susceptibility to melanoma. Melanoma Res. 2008;18:330-5 pubmed publisher
    ..93 to 1.03. We did not find significant results for the SNPs in the other four genes. These data suggest the involvement of IL-6R in melanoma development. Further studies are needed to confirm these findings. ..
  23. Yamasaki K, Taga T, Hirata Y, Yawata H, Kawanishi Y, Seed B, et al. Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor. Science. 1988;241:825-8 pubmed
    ..The cytoplasmic domain of approximately 82 amino acids lacks a tyrosine/kinase domain, unlike other growth factor receptors. ..
  24. Wilk J, Walter R, Laramie J, Gottlieb D, O Connor G. Framingham Heart Study genome-wide association: results for pulmonary function measures. BMC Med Genet. 2007;8 Suppl 1:S8 pubmed
    ..These and other observed associations warrant replication studies. This resource of GWA results for pulmonary function measures is publicly available at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite. ..
  25. Qi L, Rifai N, Hu F. Interleukin-6 receptor gene variations, plasma interleukin-6 levels, and type 2 diabetes in U.S. Women. Diabetes. 2007;56:3075-81 pubmed
    ..The strong associations between IL6R genetic variability and IL-6 concentrations deserve further investigation. ..
  26. Reich D, Patterson N, Ramesh V, De Jager P, McDonald G, Tandon A, et al. Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels. Am J Hum Genet. 2007;80:716-26 pubmed
    ..0x10-12 for IL-6 SR, and P<2.0x10-9 for IL-6. These results also serve as an important proof of principle, showing that admixture mapping can not only coarsely localize but can also fine map a phenotypically important variant. ..
  27. Schuster B, Kovaleva M, Sun Y, Regenhard P, Matthews V, Grötzinger J, et al. Signaling of human ciliary neurotrophic factor (CNTF) revisited. The interleukin-6 receptor can serve as an alpha-receptor for CTNF. J Biol Chem. 2003;278:9528-35 pubmed
    ..Engineering a CNTFR-specific human CNTF variant may therefore be a prerequisite to improving the safety profile of CNTF. ..
  28. Kluck P, Wiegant J, Jansen R, Bolk M, Raap A, Willemze R, et al. The human interleukin-6 receptor alpha chain gene is localized on chromosome 1 band q21. Hum Genet. 1993;90:542-4 pubmed
    ..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. ..
  29. Escobar Morreale H, Calvo R, Villuendas G, Sancho J, San Millan J. Association of polymorphisms in the interleukin 6 receptor complex with obesity and hyperandrogenism. Obes Res. 2003;11:987-96 pubmed
    ..Our present results further suggest that proinflammatory genotypes are involved in the pathogenesis of these common metabolic disorders. ..
  30. Shariat S, Kattan M, Traxel E, Andrews B, Zhu K, Wheeler T, et al. Association of pre- and postoperative plasma levels of transforming growth factor beta(1) and interleukin 6 and its soluble receptor with prostate cancer progression. Clin Cancer Res. 2004;10:1992-9 pubmed
    ..After prostate removal, postoperative TGF-beta(1) level increases in value over preoperative levels for the prediction of disease progression. ..
  31. Horiuchi S, Koyanagi Y, Zhou Y, Miyamoto H, Tanaka Y, Waki M, et al. Soluble interleukin-6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated through an alternative splicing mechanism. Eur J Immunol. 1994;24:1945-8 pubmed
    ..Our results indicate that active deletion of the TM domain by alternative splicing of mRNA represents one mechanism for release of sIL-6R into the culture supernatants of cells, or into serum or urine. ..
  32. Garbers C, Monhasery N, Aparicio Siegmund S, Lokau J, Baran P, Nowell M, et al. The interleukin-6 receptor Asp358Ala single nucleotide polymorphism rs2228145 confers increased proteolytic conversion rates by ADAM proteases. Biochim Biophys Acta. 2014;1842:1485-94 pubmed publisher
    ..In conclusion, increased IL-6R ectodomain shedding is a mechanistic explanation for the increased serum IL-6R levels found in persons homozygous for the rs2228145 IL-6R Asp358Ala variant. ..
  33. Boulanger M, Chow D, Brevnova E, Garcia K. Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex. Science. 2003;300:2101-4 pubmed
    ..The quaternary structures of other IL-6/IL-12 family signaling complexes are likely constructed by means of a similar topological blueprint. ..
  34. Ferreira M, Matheson M, Duffy D, Marks G, Hui J, Le Souef P, et al. Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet. 2011;378:1006-14 pubmed publisher
    ..National Health and Medical Research Council of Australia. A full list of funding sources is provided in the webappendix. ..
  35. Wang H, Zhang Z, Chu W, Hale T, Cooper J, Elbein S. Molecular screening and association analyses of the interleukin 6 receptor gene variants with type 2 diabetes, diabetic nephropathy, and insulin sensitivity. J Clin Endocrinol Metab. 2005;90:1123-9 pubmed
    ..IL-6R is not likely to explain the linkage to diabetes in this region, but our work supports a minor role of variants in T2DM risk and suggests that sequence variants may alter IL-6R mRNA levels and possibly levels of soluble IL-6R. ..
  36. Davies R, Wells G, Stewart A, Erdmann J, Shah S, Ferguson J, et al. A genome-wide association study for coronary artery disease identifies a novel susceptibility locus in the major histocompatibility complex. Circ Cardiovasc Genet. 2012;5:217-25 pubmed publisher
    ..Further laboratory studies will be required to understand the biological basis of this association and identify the causative allele(s). ..
  37. Ridker P, Pare G, Parker A, Zee R, Danik J, Buring J, et al. Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study. Am J Hum Genet. 2008;82:1185-92 pubmed publisher
  38. Song Y, Miyaki K, Araki J, Zhang L, Omae K, Muramatsu M. The interaction between the interleukin 6 receptor gene genotype and dietary energy intake on abdominal obesity in Japanese men. Metabolism. 2007;56:925-30 pubmed
    ..030). We concluded that the IL6R Asp358Ala (T/G) polymorphism appears to interact with energy intake and affect abdominal obesity in Japanese men. The interaction of this genotype and energy intake warrants further study. ..
  39. Wypasek E, Potaczek D, Lamplmayr M, Sadowski J, Undas A. Interleukin-6 receptor Asp358Ala gene polymorphism is associated with plasma C-reactive protein levels and severity of aortic valve stenosis. Clin Chem Lab Med. 2014;52:1049-56 pubmed publisher
    ..8 (0.6-1.0) vs. 0.7 (0.5-0.9) cm2, p=0.005]. Our study is the first to show that the presence of the IL-6R 358Ala allele in AS patients is associated with attenuated systemic inflammatory state and less severe AS. ..
  40. Fragiadaki K, Tektonidou M, Konsta M, Chrousos G, Sfikakis P. Sleep disturbances and interleukin 6 receptor inhibition in rheumatoid arthritis. J Rheumatol. 2012;39:60-2 pubmed publisher
    ..08). Improvement of sleep quality after tocilizumab treatment in patients with RA does not appear to directly result from decreased disease activity, further suggesting that aberrant IL-6 regulation is associated with sleep disturbances. ..
  41. van Adrichem A, Wennerberg K. MgcRacGAP inhibition stimulates JAK-dependent STAT3 activity. FEBS Lett. 2015;589:3859-65 pubmed publisher
    ..Finally, we demonstrated that MINC1-induced STAT3 activation likely is due to increased STAT3 phosphorylation caused by a Rac1-PAR3-IL6-IL6R-JAK2 mediated autocrine/paracrine mechanism. ..
  42. Sansone P, Ceccarelli C, Berishaj M, Chang Q, Rajasekhar V, Perna F, et al. Self-renewal of CD133(hi) cells by IL6/Notch3 signalling regulates endocrine resistance in metastatic breast cancer. Nat Commun. 2016;7:10442 pubmed publisher
    ..Thus, HT induces an OXPHOS metabolic editing of luminal breast cancers, paradoxically establishing HT-driven self-renewal of dormant CD133(hi)/ER(lo) cells mediating metastatic progression, which is sensitive to dual targeted therapy. ..
  43. Bettaccini A, Baj A, Accolla R, Basolo F, Toniolo A. Proliferative activity of extracellular HIV-1 Tat protein in human epithelial cells: expression profile of pathogenetically relevant genes. BMC Microbiol. 2005;5:20 pubmed
    ..These effects may favor virus replication and may facilitate the mother-to-child transmission of virus. ..
  44. Ogawa K, Kawahara M, Nagamune T. Construction of unnatural heterodimeric receptors based on IL-2 and IL-6 receptor subunits. Biotechnol Prog. 2013;29:1512-8 pubmed publisher
    ..Further extension of this approach may attain a creative design of artificial receptor pairs that have distinct signaling properties when compared with natural receptors. ..
  45. Ruggeri R, Villari D, Simone A, Scarfi R, Attard M, Orlandi F, et al. Co-expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) in thyroid nodules is associated with co-expression of CD30 ligand/CD30 receptor. J Endocrinol Invest. 2002;25:959-66 pubmed
    ..In the normal thyroid tissue, colloid nodules, and another subset of benign and malignant thyroid nodules, IL-6 expression is under control of signals other than CD30L/CD30. ..
  46. Johnson N, Brezinova J, Stephens E, Burbridge E, Freeman M, Adrain C, et al. Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis. Sci Rep. 2017;7:7283 pubmed publisher
    ..The expression profiles and identity of the substrates implicate RHBDL2 in physiological or pathological processes affecting epithelial homeostasis. ..
  47. van Hamburg J, Tas S. Molecular mechanisms underpinning T helper 17 cell heterogeneity and functions in rheumatoid arthritis. J Autoimmun. 2018;87:69-81 pubmed publisher
    ..Understanding these mechanisms creates great potential to identify and select novel therapeutic targets which could improve current therapies or lead to development of new treatment strategies in RA. ..
  48. Jablonska E, Marcinczyk M. Role of interleukin-15 and interleukin-18 in the secretion of sIL-6R and sgp130 by human neutrophils. Mediators Inflamm. 2003;12:179-83 pubmed
  49. Galicia J, Tai H, Komatsu Y, Shimada Y, Akazawa K, Yoshie H. Polymorphisms in the IL-6 receptor (IL-6R) gene: strong evidence that serum levels of soluble IL-6R are genetically influenced. Genes Immun. 2004;5:513-6 pubmed
    ..0082) compared with the A allele carriers. This could be attributed to the linkage disequilibrium (D'=0.54, chi2=51.3, P<0.0001) between the -183G/A and the 48892A/C gene polymorphisms. ..
  50. Ebihara N, Matsuda A, Nakamura S, Matsuda H, Murakami A. Role of the IL-6 classic- and trans-signaling pathways in corneal sterile inflammation and wound healing. Invest Ophthalmol Vis Sci. 2011;52:8549-57 pubmed publisher
    ..To investigate the role of the IL-6 classic- and trans-signaling pathways in corneal sterile inflammation and wound healing...
  51. Fabris M, Quartuccio L, Lombardi S, Saracco M, Atzeni F, Carletto A, et al. The CC homozygosis of the -174G>C IL-6 polymorphism predicts a lower efficacy of rituximab therapy in rheumatoid arthritis. Autoimmun Rev. 2012;11:315-20 pubmed publisher
    ..No definite association between gene polymorphisms and IL-6 serum levels was noticed. Present results suggest a possible role for IL-6 genotyping to better plan treatment with RTX in RA, and larger studies are worthwhile. ..
  52. Borelli B, Zarone F, Rivieccio V, Riccitiello F, Simeone M, Sorrentino R, et al. Polyacrylic resins regulate transcriptional control of interleukin-6, gp80, and gp130 genes in human gingival fibroblasts. J Oral Sci. 2017;59:87-91 pubmed publisher
    ..This study focused on IL-6 and activation of its receptors gp80 and gp130 in human gingival fibroblasts in order to assess the effects of the commercial acid resins Jet Kit, ..
  53. Eichten A, Su J, Adler A, Zhang L, Ioffe E, Parveen A, et al. Resistance to Anti-VEGF Therapy Mediated by Autocrine IL6/STAT3 Signaling and Overcome by IL6 Blockade. Cancer Res. 2016;76:2327-39 pubmed publisher
    ..Cancer Res; 76(8); 2327-39. ©2016 AACR. ..
  54. Klouche M, Bhakdi S, Hemmes M, Rose John S. Novel path to activation of vascular smooth muscle cells: up-regulation of gp130 creates an autocrine activation loop by IL-6 and its soluble receptor. J Immunol. 1999;163:4583-9 pubmed
  55. Bharadwaj U, Marin Muller C, Li M, Chen C, Yao Q. Mesothelin overexpression promotes autocrine IL-6/sIL-6R trans-signaling to stimulate pancreatic cancer cell proliferation. Carcinogenesis. 2011;32:1013-24 pubmed publisher
    ..The close correlation between MSLN and IL-6 provides a new rationale for combination therapy for effective control of MSLN-overexpressing PCs. ..
  56. Tumu V, Govatati S, Guruvaiah P, Deenadayal M, Shivaji S, Bhanoori M. An interleukin-6 gene promoter polymorphism is associated with polycystic ovary syndrome in South Indian women. J Assist Reprod Genet. 2013;30:1541-6 pubmed publisher
    ..The current study was aimed to evaluate the association between IL-6 gene -174 G/C promoter polymorphism and Polycystic Ovary Syndrome in South Indian women...
  57. Li S, Fu X, Wu T, Yang L, Hu C, Wu R. Role of Interleukin-6 and Its Receptor in Endometriosis. Med Sci Monit. 2017;23:3801-3807 pubmed
    ..CONCLUSIONS Disorders involving IL-6 and IL-6R are correlated with the etiology of endometriosis. An increase in sIL-6R in peritoneal fluid promotes the development of endometriosis by enhancing the bioactivity of IL-6. ..
  58. Schumacher N, Schmidt S, Schwarz J, Dohr D, Lokau J, Scheller J, et al. Circulating Soluble IL-6R but Not ADAM17 Activation Drives Mononuclear Cell Migration in Tissue Inflammation. J Immunol. 2016;197:3705-3715 pubmed
    ..Our data suggest that this infiltrating sIL-6R, which is needed for IL-6 trans-signaling, is involved in the controlled resolution of an acute inflammatory episode. ..
  59. Gomez M, Sokol S, Muir A, Soong G, Bastien J, Prince A. Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling. J Immunol. 2005;175:1930-6 pubmed
    ..Thus, bacteria are physiological activators of TACE expression, which provides a mechanism to regulate inflammatory signaling that is initiated by airway epithelial cells. ..
  60. Zhang T, Kee W, Seow K, Fung W, Cao X. The coiled-coil domain of Stat3 is essential for its SH2 domain-mediated receptor binding and subsequent activation induced by epidermal growth factor and interleukin-6. Mol Cell Biol. 2000;20:7132-9 pubmed
    ..Finally, we demonstrate a direct binding of Stat3 to the receptor. Taken together, our data reveal a novel role for the coiled-coil domain that regulates the early events in Stat3 activation and function. ..
  61. Skiniotis G, Boulanger M, Garcia K, Walz T. Signaling conformations of the tall cytokine receptor gp130 when in complex with IL-6 and IL-6 receptor. Nat Struct Mol Biol. 2005;12:545-51 pubmed
    ..Variation in the receptor bend angles suggests a possible conformational transition from open to closed states upon ligand binding; this transition is probably representative of the other tall cytokine receptors. ..
  62. Tsukamoto H, Fujieda K, Hirayama M, Ikeda T, Yuno A, Matsumura K, et al. Soluble IL6R Expressed by Myeloid Cells Reduces Tumor-Specific Th1 Differentiation and Drives Tumor Progression. Cancer Res. 2017;77:2279-2291 pubmed publisher
    ..Overall, this work provides a mechanistic rationale for sIL6R targeting to improve the efficacy of T-cell-mediated cancer immunotherapy. Cancer Res; 77(9); 2279-91. ©2017 AACR. ..
  63. Hwang Y, Yu H, Kim D, Jang J, Kim H, Kang I, et al. Expansion of CD8(+) T cells lacking the IL-6 receptor ? chain in patients with coronary artery diseases (CAD). Atherosclerosis. 2016;249:44-51 pubmed publisher
    ..Our findings suggest the possible involvement of expanded CD8(+)IL-6R?(low) EM T cells in CAD through their pro-inflammatory and highly cytotoxic capacities. ..
  64. Schumacher N, Meyer D, Mauermann A, von der Heyde J, Wolf J, Schwarz J, et al. Shedding of Endogenous Interleukin-6 Receptor (IL-6R) Is Governed by A Disintegrin and Metalloproteinase (ADAM) Proteases while a Full-length IL-6R Isoform Localizes to Circulating Microvesicles. J Biol Chem. 2015;290:26059-71 pubmed publisher
    ..Instead, we found full-length IL-6R on circulating microvesicles, establishing microvesicle release as a novel mechanism for sIL-6R generation. ..
  65. Burger M, De Wet H, Collins M. Interleukin and growth factor gene variants and risk of carpal tunnel syndrome. Gene. 2015;564:67-72 pubmed publisher
    ..This highlights that interleukin and growth factor gene variants should also be considered, in addition to the extracellular matrix proteins, for future research in determining the aetiology of CTS. ..
  66. Cui X, Rouhani F, Hawari F, Levine S. An aminopeptidase, ARTS-1, is required for interleukin-6 receptor shedding. J Biol Chem. 2003;278:28677-85 pubmed
    ..We propose that ARTS-1 is a multifunctional aminopeptidase that may modulate inflammatory events by promoting IL-6Ralpha and TNFR1 shedding. ..
  67. Robson Ansley P, Cockburn E, Walshe I, Stevenson E, Nimmo M. The effect of exercise on plasma soluble IL-6 receptor concentration: a dichotomous response. Exerc Immunol Rev. 2010;16:56-76 pubmed
    ..Our data suggests an association between sIL-6R, perception of pain and reduced peak muscle performance post-EIMD but further investigation is warranted to explore this relationship and implications for exercise performance. ..
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    ..consists of an ubiquitously expressed membrane transducing element (gp130) and of the specific element IL-6R-alpha (gp80), present only on hepatocytes and some leukocyte subsets...