Genomes and Genes
Gene Symbol: Il6r
Description: interleukin 6 receptor
Alias: IL6R1, Il6ra, interleukin-6 receptor subunit alpha, IL-6 receptor subunit alpha, IL-6R 1, IL-6R subunit alpha, IL-6R-alpha, IL-6RA, interleukin 6 receptor, alpha
- Mitnick M, Grey A, Masiukiewicz U, Bartkiewicz M, Rios Velez L, Friedman S, et al. Parathyroid hormone induces hepatic production of bioactive interleukin-6 and its soluble receptor. Am J Physiol Endocrinol Metab. 2001;280:E405-12 pubmed
- Zorina Y, Iyengar R, Bromberg K. Cannabinoid 1 receptor and interleukin-6 receptor together induce integration of protein kinase and transcription factor signaling to trigger neurite outgrowth. J Biol Chem. 2010;285:1358-70 pubmed publisher..These results provide a mechanism where multiple protein kinases and transcription factors interact to integrate signals from G protein-coupled and cytokine receptor to evoke neurite outgrowth in Neuro2A cells. ..
- Baumann M, Baumann H, Fey G. Molecular cloning, characterization and functional expression of the rat liver interleukin 6 receptor. J Biol Chem. 1990;265:19853-62 pubmed..Therefore, both IL6-R mRNA species code for functionally active receptor, depending on the target cell, but only the longer mRNA species coded for significant receptor levels in human hepatoma cell lines. ..
- Schuster B, Meinert W, Rose John S, Kallen K. The human interleukin-6 (IL-6) receptor exists as a preformed dimer in the plasma membrane. FEBS Lett. 2003;538:113-6 pubmed..When lysates of COS-7 cells expressing only one of the IL-6R variants are mixed, spontaneous dimerization occurs. Thus, the IL-6R dimer observed in the crystal structure represents a physiologically occurring phenomenon. ..
- Kawashima M, Shoji J, Nakajima M, Kamura Y, Sato Y. Soluble IL-6 receptor in vitreous fluid of patients with proliferative diabetic retinopathy. Jpn J Ophthalmol. 2007;51:100-4 pubmed..34, P < 0.05). We conclude that the level of sIL-6R in vitreous fluid can be considered as a biomarker of PDR. ..
- Abbatecola A, Ferrucci L, Grella R, Bandinelli S, Bonafe M, Barbieri M, et al. Diverse effect of inflammatory markers on insulin resistance and insulin-resistance syndrome in the elderly. J Am Geriatr Soc. 2004;52:399-404 pubmed..448; P=.015) were associated with IRS, and higher sIL-6R plasma levels continued to correlate negatively with IRS. Different inflammatory markers are associated with a diverse effect on IR and IRS in elderly nondiabetic subjects. ..
- 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. ..
- Watanabe D, Yoshimura R, Khalil M, Yoshida K, Kishimoto T, Taga T, et al. Characteristic localization of gp130 (the signal-transducing receptor component used in common for IL-6/IL-11/CNTF/LIF/OSM) in the rat brain. Eur J Neurosci. 1996;8:1630-40 pubmed
- Yamashita S, Kato R, Kobayashi K, Hisasue S, Arai Y, Tsukamoto T. Inhibition of interleukin-6 attenuates erectile dysfunction in a rat model of nerve-sparing radical prostatectomy. J Sex Med. 2011;8:1957-64 pubmed publisher..Inhibition of IL-6 bioactivity attenuated ED following CN dissection. Thus, the suppression of excess inflammatory responses in the acute phase may lead to improvements in ED occurring after nerve-sparing radical prostatectomy. ..
- Chen L, QIAN Y, Cai M, LI Z, BAI H, SHI B. [Role of the activation of interleukin-6/STAT3 in cholangiocyte proliferation induced by cold ischemia reperfusion and injury]. Zhonghua Wai Ke Za Zhi. 2009;47:863-7 pubmed..IL-6/STAT3 pathway might participate to initiate cholangiocytes regeneration after cold ischemia and preservation injury, which might benefit biliary recovery after liver transplantation. ..
- Lehtimäki K, Peltola J, Koskikallio E, Keranen T, Honkaniemi J. Expression of cytokines and cytokine receptors in the rat brain after kainic acid-induced seizures. Brain Res Mol Brain Res. 2003;110:253-60 pubmed..In addition, the activity of IL-6 and LIF signaling pathways may be influenced by increased expression of their receptors after seizures. ..
- Jones S, Scheller J, Rose John S. Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. J Clin Invest. 2011;121:3375-83 pubmed publisher..Attention will be given to the role of the soluble IL-6R, and we will provide a perspective into the clinical blockade of IL-6 activity in autoimmunity, inflammation, and cancer. ..
- 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. ..
- Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T. Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell. 1990;63:1149-57 pubmed..A cloned gp130 could associate with a complex of IL-6 and soluble IL-6-R and transduce the growth signal when expressed in a murine IL-3-dependent cell line. ..
- 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. ..
- 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..BMD) and body mass index (BMI) linkage studies identified a locus at 1q21-23, where the interleukin-6 receptor (IL6R) gene is located. The IL6R and the gp130 receptors are the mediators of IL6 action...
- Fiorillo M, Toniatti C, Van Snick J, Ciliberto G. Expression of the murine interleukin 6 receptor in hepatoma cells: the intracytoplasmic domain is not required for interleukin 6 signal transduction. Eur J Immunol. 1992;22:799-804 pubmed..e. CRP promoter activation), but that the last 40 amino acids contribute to maximal IL6 response in these cells. ..
- Mehra R, Storfer Isser A, Kirchner H, Johnson N, Jenny N, Tracy R, et al. Soluble interleukin 6 receptor: A novel marker of moderate to severe sleep-related breathing disorder. Arch Intern Med. 2006;166:1725-31 pubmed..Further investigation of this biomarker may provide insight into SRBD-related inflammation. ..
- Chang X, Qin Y, Jin Z, Xi T, Yang X, Lu Z, et al. Interleukin-6 (IL-6) mediated the increased contraction of distal colon in streptozotocin-induced diabetes in rats via IL-6 receptor pathway. Int J Clin Exp Pathol. 2015;8:4514-24 pubmed..The expression of IL-6 Î±-receptor increased in diabetes rats. These results indicate that diabetes rats show an increase in the contractions of distal colon partly via the IL-6-IL-6 receptor pathway. ..
- Hoffmann R, Henninger H, Schulze Specking A, Decker K. Regulation of interleukin-6 receptor expression in rat Kupffer cells: modulation by cytokines, dexamethasone and prostaglandin E2. J Hepatol. 1994;21:543-50 pubmed..These results suggest the existence of control mechanisms involving several soluble mediators that help balance the level of interleukin-6-R mRNA in rat liver macrophages. ..
- Inomata Y, Hirata A, Yonemura N, Koga T, Kido N, Tanihara H. Neuroprotective effects of interleukin-6 on NMDA-induced rat retinal damage. Biochem Biophys Res Commun. 2003;302:226-32 pubmed..Western blotting studies demonstrated upregulation of gp130 expression in the NMDA-injected retina. Present studies suggest that IL-6 combined with sIL-6R provides a neuroprotective effect on NMDA-induced retinal damage. ..
- Wang T, Wang B, Zhao H, Kuang F, Fan J, Duan X, et al. Lipopolysaccharide up-regulates IL-6R alpha expression in cultured leptomeningeal cells via activation of ERK1/2 pathway. Neurochem Res. 2008;33:1901-10 pubmed publisher..Moreover, ERK1/2 pathway seems to be involved in the process of LPS-induced IL-6R alpha up-regulation in leptomeningeal cells. ..
- Chen X, Zhang M, Liao M, Graner M, Wu C, Yang Q, et al. Reduced Th17 response in patients with tuberculosis correlates with IL-6R expression on CD4+ T Cells. Am J Respir Crit Care Med. 2010;181:734-42 pubmed publisher..tuberculosis infection. Suppression of Th17 response through down-regulation of IL-6R expression may be an important mechanism in the development of active TB. ..
- Vermes C, Jacobs J, Zhang J, Firneisz G, Roebuck K, Glant T. Shedding of the interleukin-6 (IL-6) receptor (gp80) determines the ability of IL-6 to induce gp130 phosphorylation in human osteoblasts. J Biol Chem. 2002;277:16879-87 pubmed..This unique mechanism provides the flexibility for osteoblasts to control their own responsiveness to IL-6 via the activation of an IL-6R sheddase, resulting in an immediate production of functionally active osteoblast-derived sIL-6R. ..
- Helwig B, Musch T, Craig R, Kenney M. Increased interleukin-6 receptor expression in the paraventricular nucleus of rats with heart failure. Am J Physiol Regul Integr Comp Physiol. 2007;292:R1165-73 pubmed..Rather the increased IL-6 levels characteristic of HF may alter PVN-mediated physiological responses via enhanced expression of the IL-6R. ..
- Szabo Fresnais N, Lefebvre F, Germain A, Fischmeister R, Pomerance M. A new regulation of IL-6 production in adult cardiomyocytes by beta-adrenergic and IL-1 beta receptors and induction of cellular hypertrophy by IL-6 trans-signalling. Cell Signal. 2010;22:1143-52 pubmed publisher..The IL-6 soluble receptor may thus serve as a switch for IL-6 to activate STAT3 phosphorylation and hypertrophy. ..
- Bagli M, Papassotiropoulos A, Hampel H, Becker K, Jessen F, Burger K, et al. 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. Eur Arch Psychiatry Clin Neurosci. 2003;253:44-8 pubmed..We conclude that plasma and CSF levels of sIL-6R are significantly increased in AD patients and that the magnitude of increase is determined by the IL-6 genotype. ..
- Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond). 2012;122:143-59 pubmed publisher..In the present review, we first summarize the IL-6/IL-6R system and IL-6 signal transduction, and then go on to discuss the physiological and pathological roles of IL-6. ..
- Matsushita K, Iwanaga S, Oda T, Kimura K, Shimada M, Sano M, et al. Interleukin-6/soluble interleukin-6 receptor complex reduces infarct size via inhibiting myocardial apoptosis. Lab Invest. 2005;85:1210-23 pubmed..The IL-6/soluble IL-6 receptor complex inhibits cardiomyocyte apoptosis in reperfused acute myocardial infarction. It possibly reduces irreversible reperfusion injury. ..
- 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. ..
- Bensadoun J, de Almeida L, Dreano M, Aebischer P, Deglon N. Neuroprotective effect of interleukin-6 and IL6/IL6R chimera in the quinolinic acid rat model of Huntington's syndrome. Eur J Neurosci. 2001;14:1753-61 pubmed..Interleukin-6, another member of the cytokine family, and the chimeric molecule (IL6/IL6R) in which interleukin-6 and its soluble receptor are fused, have been shown to exert trophic action on various ..
- Legendre F, Dudhia J, Pujol J, Bogdanowicz P. JAK/STAT but not ERK1/ERK2 pathway mediates interleukin (IL)-6/soluble IL-6R down-regulation of Type II collagen, aggrecan core, and link protein transcription in articular chondrocytes. Association with a down-regulation of SOX9 expression. J Biol Chem. 2003;278:2903-12 pubmed..These IL-6 effects might contribute to the phenotype loss of chondrocytes in joint diseases and the alteration of articular cartilage associated with this pathology. ..
- Zhang J, Gao Y, Shen Y, Li K. Asymmetrical release of interleukin-6 by cultured cerebral cortical astrocytes treated with lipopolysaccharide. Indian J Med Res. 2009;129:164-9 pubmed..05). The results showed asymmetrical release of brain IL-6 by cerebral cortical astrocytes to the inflammatory insults both in protein and mRNA levels. ..
- Malavazos A, Corsi M, Ermetici F, Coman C, Sardanelli F, Rossi A, et al. Proinflammatory cytokines and cardiac abnormalities in uncomplicated obesity: relationship with abdominal fat deposition. Nutr Metab Cardiovasc Dis. 2007;17:294-302 pubmed
- Finotto S, Eigenbrod T, Karwot R, Boross I, Doganci A, Ito H, et al. Local blockade of IL-6R signaling induces lung CD4+ T cell apoptosis in a murine model of asthma via regulatory T cells. Int Immunol. 2007;19:685-93 pubmed..Local targeting of IL-6R signaling could be a novel approach for inducing Th2 T cell death in allergic airways via regulatory T cells. ..
- Li Y, Wang Y, Qi L. [Determination of serum soluble interleukin-6 receptor and soluble gp130 levels in patient with pregnancy induced hypertension and its significance]. Zhonghua Fu Chan Ke Za Zhi. 2001;36:18-9 pubmed..There was significant difference (P < 0.01). There was no difference in sIL-6R and sgp130 levels between control groups (P > 0.05). Serum sIL-6R and sgp130 levels are related to the development of pregnancy induced hypertension. ..
- Griffiths M, Encinas J, Remmers E, Kuchroo V, Wilder R. Mapping autoimmunity genes. Curr Opin Immunol. 1999;11:689-700 pubmed..Candidate genes are being identified. Polymorphic alleles associated with these chromosomal segments may represent predisposing genetic elements common to a number of human diseases with very different clinical presentations. ..
- Zvibel I, Brill S, Kariv R, Traister A, Golan T, Chebath J, et al. Chimeric molecule IL-6/soluble IL-6 receptor is a potent mitogen for fetal hepatocytes. J Cell Physiol. 2004;200:245-52 pubmed..In conclusion, IL-6c stimulated proliferation and affected gene expression in fetal hepatocytes in culture. ..
- Marta R, Goette N, Lev P, Chazarreta C, Pirola C, Molinas F. Normal platelets possess the soluble form of IL-6 receptor. Cytokine. 2005;29:13-7 pubmed..Besides, since we could not find IL-6R on platelet membrane, the potentiating effect of IL-6 on platelet function could be explained through binding of IL-6sR/IL-6 complex to platelet membrane gp130. ..
- 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..through a heterodimeric receptor consisting of two membrane-bound glycoproteins: an 80-kDa IL-6 binding unit (IL6R-alpha) and a 130-kDa IL-6 signal transducer (gp130)...
- Gallucci R, Sloan D, O Dell S, Reinke L. Differential expression of liver interleukin-6 receptor-alpha in female versus male ethanol-consuming rats. Alcohol Clin Exp Res. 2004;28:365-73 pubmed..Given the association of inflammation with ethanol-induced liver damage, these data may offer insight into a possible mechanism by which females develop more severe ALD than males. ..
- Linard C, Marquette C, Mathieu J, Pennequin A, Clarençon D, Mathe D. Acute induction of inflammatory cytokine expression after gamma-irradiation in the rat: effect of an NF-kappaB inhibitor. Int J Radiat Oncol Biol Phys. 2004;58:427-34 pubmed..In vivo, irradiation induced a cascade of inflammatory responses that involved the transcription factor NF-kappaB; this inflammation was reduced by CAPE treatment. ..
- Petrinović Doresić J, Mazuran R, Henc Petrinović L, Kuzmanovic B, Jovicic A. Interleukin 6 and its soluble receptor are elevated in aqueous humor of patients with uveitis. Ocul Immunol Inflamm. 1999;7:75-84 pubmed..Low levels of sIL-6R in AH compared to those found in serum suggest the presence of active local regulatory mechanisms that require further investigation. ..
- Fulop A, Pocsik E, Brozik M, Karabelyos C, Kiss A, Novak I, et al. Hepatic regeneration induces transient acute phase reaction: systemic elevation of acute phase reactants and soluble cytokine receptors. Cell Biol Int. 2001;25:585-92 pubmed..These data suggest the involvement of both acute phase proteins and soluble cytokine receptors in the regulation of liver regeneration. ..
- Rival C, Theas M, Guazzone V, Lustig L. Interleukin-6 and IL-6 receptor cell expression in testis of rats with autoimmune orchitis. J Reprod Immunol. 2006;70:43-58 pubmed..Our results suggest that IL-6 and IL-6R may be involved in the pathogenesis of autoimmune orchitis by promoting testicular inflammation and germ cell apoptosis...
- Deten A, Volz H, Briest W, Zimmer H. Cardiac cytokine expression is upregulated in the acute phase after myocardial infarction. Experimental studies in rats. Cardiovasc Res. 2002;55:329-40 pubmed
- Brazda V, Klusáková I, Hradilová Svíženská I, Dubovy P. Dynamic response to peripheral nerve injury detected by in situ hybridization of IL-6 and its receptor mRNAs in the dorsal root ganglia is not strictly correlated with signs of neuropathic pain. Mol Pain. 2013;9:42 pubmed publisher..Possible functional involvement of IL-6 signaling is discussed. ..
- Gulko P, Kawahito Y, Remmers E, Reese V, Wang J, Dracheva S, et al. Identification of a new non-major histocompatibility complex genetic locus on chromosome 2 that controls disease severity in collagen-induced arthritis in rats. Arthritis Rheum. 1998;41:2122-31 pubmed..This rat model should facilitate positional cloning and functional characterization of regulatory genes that may play a role in several forms of autoimmune disease, including rheumatoid arthritis. ..
- Bossowski A, Urban M, Koput A, Gardziejczyk M, Wysocka J, Kreczko S. [Serum levels of interleukin 6 (IL-6) and soluble IL-6 receptor (sIL-6R) in children and adolescents with Graves-Basedow disease]. Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw. 1999;5:85-93 pubmed..No correlation was revealed between the level of thyroid hormones and the concentration of cytokines and adhesion molecules. ..
- Ouellet J, Berthiaume M, Corriveau S, Rola Pleszczynski M, Pasquier J. Effect of interleukin-6 receptor blockade on feto-maternal outcomes in a rat model of intrauterine inflammation. J Obstet Gynaecol Res. 2013;39:1456-64 pubmed publisher..06). Paradoxically, the association of pregnancy, inflammation and anti-IL-6R increases the inflammatory effects of LPS. ..