• Experimental data have implicated gp130, a subunit of the receptor for interleukin-6 (IL-6)-related cytokines, in the regulation of proliferation and apoptosis of cardiomyocytes and vascular smooth muscle cells (VSMC). (uni-luebeck.de)
  • Gp130 serves as the signal transducing receptor subunit for the IL-6-type cytokines consisting of interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), new neurotrophin factor-1 (NNT-1), IL-27, cardiotrophin-1 (CT-1), and cardiotrophin like cytokine (CLC) (2 - 5). (rndsystems.com)
  • Binding affinity is increased by the ligand-induced association of LIF R alpha with the signal transducing subunit gp130 (6, 7). (rndsystems.com)
  • Upon binding of IL-6 to the receptor (alpha subunit), gp130 is homodimerized and is subsequently involved in down-stream signal processes binding tyrosine kinases and activating STAT1 and STAT3 transcriptional factors. (sbhsciences.com)
  • IL-6 exerts its action via a cell surface receptor which consists of two subunits, an 80 kDa ligand binding subunit (gp80) of 468 amino acids and a 130 kDa signal transducing protein (gp130) of 896 amino acid residues. (thermofisher.com)
  • The IL6 receptor is a protein complex consisting of this protein and interleukin 6 signal transducer (IL6ST/GP130/IL6-beta), a receptor subunit also shared by many other cytokines. (thermofisher.com)
  • Oncostatin M Oncostatin M (OSM) is an IL-6 family cytokine, characterized by the shared gp130 receptor subunit. (brinda.info)
  • Hyper-IL-6 is a fusion protein of the four-helical cytokine Interleukin-6 and the soluble Interleukin-6 receptor which are covalently linked by a flexible peptide linker. (wikipedia.org)
  • Therefore, the generation of the soluble Interleukin-6 receptor enables cells to respond to Interleukin-6, which in the absence of soluble Interleukin-6 receptor would be completely unresponsive to the cytokine. (wikipedia.org)
  • However, the activity of these cytokines are modulated by soluble cytokine receptors and cytokines with anti-inflammatory activities, and in the present study several of these interacting factors were examined simultaneously in 38 CHF patients with various degrees of heart failure and in 21 healthy controls. (nih.gov)
  • The abnormalities in the cytokine network were most pronounced in patients with the most severe heart failure, and several of the immunologic parameters, in particular soluble gp130, were correlated with variables reflecting deranged hemodynamic status. (nih.gov)
  • LIF R alpha binds the pleiotropic cytokine LIF with low affinity, and the soluble isoform retains LIF-binding activity (5). (rndsystems.com)
  • Patients with CHF had increased plasma concentrations of tumor necrosis factor (TNF)alpha, interleukin-6, soluble TNF receptors and the soluble interleukin-6 receptor, glycoprotein (gp)130. (nih.gov)
  • They also had elevated ratios of TNFalpha/soluble TNF receptors and interleukin-6/soluble gp130 as well as enhanced interleukin-6 bioactivity in serum, suggesting inflammatory net effects. (nih.gov)
  • gp130 associates with different ligand-specific receptors to form signaling receptor complexes for the other IL-6 family ligands (1). (rndsystems.com)
  • Tocilizumab is a recombinant humanized anti-interleukin 6 (IL-6) receptor monoclonal antibody that inhibits the binding of IL-6 to both membrane and soluble IL-6 receptors, blocking thereby IL-6 signaling and dampening inflammation. (ospublishers.com)
  • When membrane protein fractions were prepared from PMNs and isolated human glomeruli, and immunoblotted with ANCA sera of NCGN patients, two bands with apparent molecular masses of 170 and 80-110 kD (gp170/80-110) were labeled in PMNs, and a 130-kD glycoprotein (gp130) in glomeruli. (rupress.org)
  • Both LIF and IL-6 [in the absence of soluble IL-6 receptor (sIL-6Rα)] activated Erk1/2, JNK1/2, p38-MAPK and PI3K signalling peaking at 20min and induced cytoprotection against simulated ischemia-reperfusion injury which was blocked by the MEK1/2 inhibitor PD98059 but not the p38-MAPK inhibitor SB203580. (ox.ac.uk)
  • Rat gp130 is synthesized as a 918 amino acid (aa) precursor with a 22 aa signal sequence, a 596 aa extracellular domain (ECD), a 22 aa transmembrane region, and a 278 aa cytoplasmic tail. (rndsystems.com)
  • The remainder of the extracellular domain however is essential for low affinity ligand binding, which consecutively triggers the association of the receptor and gp130 thus forming a high affinity binding site for IL-6. (thermofisher.com)
  • METHODS: We measured serum concentrations of soluble gp130, IL-6, the soluble IL-6 receptor, and the intima-media thickness of the common carotid artery in stroke patients (n = 48) and in elderly controls (n = 48). (uni-luebeck.de)
  • RESULTS: Soluble gp130 serum concentrations correlated with blood pressure in stroke patients and in elderly and young controls and with the intima-media thickness of the common carotid artery in stroke patients. (uni-luebeck.de)
  • CONCLUSION: Our data suggest that soluble gp130 serum concentrations are correlated with blood pressure and may reflect vascular remodeling in response to arterial hypertension. (uni-luebeck.de)
  • It was found, however, that the membrane-bound Interleukin-6 receptor can be cleaved from the cell membrane generating a soluble Interleukin-6 receptor. (wikipedia.org)
  • The soluble Interleukin-6 receptor can bind the ligand Interleukin-6 with similar affinity as the membrane-bound Interleukin-6 receptor and the complex of Interleukin-6 and the soluble Interleukin-6 receptor can bind to gp130 on cells, which only express gp130 but no Interleukin-6 receptor. (wikipedia.org)
  • The mode of signaling via the soluble Interleukin-6 receptor has been named Interleukin-6 trans-signaling whereas Interleukin-6 signaling via the membrane-bound Interleukin-6 receptor is referred to as Interleukin-6 classic signaling. (wikipedia.org)
  • IL-6 signals via binding to either the membrane bound IL-6Rα (classic signaling) or soluble (s)IL-6Ra (trans-signaling) that then form a complex with gp130 to activate the JAK/STAT signaling pathway. (jneurosci.org)
  • IL-6 can also associate with its soluble receptor (sIL-6R), activating target cells which do not express membrane bound IL-6R but only gp130 by a process called trans-signaling [86]. (brinda.info)
  • In classic signaling, IL-6 stimulates target cells via a membrane bound interleukin-6 receptor (IL-6R), which upon ligand binding associates with the signaling receptor protein gp130. (eaglebio.com)
  • In other words, LT-α has both a membrane-bound and soluble form that perform distinct roles in immune regulation. (wikidoc.org)
  • No. 551462) can be used as the capture antibody, with recombinant soluble IL-6Ra as the standard, the Biotin Mouse Anti-Human CD126 (Cat. (bdbiosciences.com)
  • Potential clinical relevance of autoantibodies to gp170/80-110 and gp130 was assessed in a preliminary trial, in which ANCA sera of patients (n = 16) with NCGN were probed with purified or recombinant antigens. (rupress.org)
  • Here, we investigate whether serum soluble gp130 concentrations correlate with blood pressure in humans, whether gp130 expression in the aorta differs between hypertensive and control rats, and whether angiotensin II or endothelin regulate gp130 expression in human VSMC. (uni-luebeck.de)
  • The anti-inflammatory activities of IL-6 are transmitted by this signaling pathway whereas proinflammatory responses of IL-6 are mediated by trans-signaling (cells expressing only gp130 respond to a complex of IL-6 bound to a soluble form of the IL-6R). (eaglebio.com)
  • The hypothesis that elevated soluble gp130 derives from the vascular system was supported by the enhanced expression of gp130 in the aortic wall of spontaneously hypertensive rats. (uni-luebeck.de)
  • We are currently testing a pharmacological compound, sgp130Fc (fused chimera of extracellular gp130 and the Fc region of IgG1), to selectively inhibit the IL-6 trans-signaling pathway to prevent the inflammation and retinal vascular dysfunction associated with diabetic retinopathy. (augusta.edu)
  • It can exert its action via a dimeric receptor composed of the IL6-R and gp130 subunits, activating the STAT3 and MAP kinase pathways. (brinda.info)
  • Building on prior findings that chronic proinflammatory IL-6 activity is primarily mediated by trans-signaling of a complex of IL-6 and soluble IL6R that engages the gp130 receptor, the researchers developed a "decoy protein," sgp130Fc (now known as olamkicept), which "exclusively blocks" IL-6 proinflammatory trans-signaling. (mdedge.com)
  • OSMR targeting by a Fc-tagged soluble OSMR-gp130 fusion protein was shown to significantly attenuate colitis in an IBD mouse model resistant to anti-TNF therapy.96 Furthermore, adenoviral transfer of OSM also reduced the severity of DSS-induced colitis.121 A Phase II clinical trial was performed for an anti-OSM humanized monoclonal antibody [GSK315234]. (bibf1120.com)
  • The soluble form of IL-6R can bind its ligand and induce cellular responses by association with gp130, thus acting as an IL-6 agonist. (sbhsciences.com)
  • So far, the soluble IL-6 receptor is unique in acting as an agonist together with its ligand. (thermofisher.com)
  • Alternative splicing generates a 90 kDa soluble form of the mouse LIF R alpha ECD (4). (rndsystems.com)
  • Both IL-6R and gp130 also occur in soluble form in biological fluids and has been purified from human serum and urine. (sbhsciences.com)
  • Interestingly, the association of IL-6 with the soluble form of IL-6R alpha is capable of eliciting a biological response in cells that express only the membrane gp130. (sbhsciences.com)
  • A soluble form of the human gp80 protein has been detected in serum and urine samples. (thermofisher.com)
  • Low concentration of a soluble form of IL6 receptor acts as an agonist of IL6 activity. (nih.gov)
  • Soluble forms of the interleukin-6 signal-transducing receptor component gp130 in human serum possessing a potential to inhibit signals through membrane-anchored gp130. (ajbm.net)
  • 9. Jones SA, Scheller J, Rose-John S. Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. (ajbm.net)
  • Expression of gp130 in Wistar-Kyoto (n = 12), spontaneously hypertensive rats (n = 12), and human VSMC was detected by real-time reverse transcription-PCR and immunohistochemistry. (uni-luebeck.de)
  • Furthermore, treatment of human VSMC with angiotensin II stimulated gp130 expression. (uni-luebeck.de)
  • Gp130 is expressed on all cells of the human body whereas the Interleukin-6 receptor is only found on few cells such as hepatocytes and some leukocytes. (wikipedia.org)
  • Detects human gp130 in direct ELISAs. (rndsystems.com)
  • Human gp130 shares 73% and 79% aa sequence identity with mouse and rat gp130, respectively. (rndsystems.com)
  • Description: Recognizes soluble and membranous human IL-6R. (thermofisher.com)
  • Since all human being cells communicate gp130 on their surface, the IL-6/sIL-6R complex can HDAC-IN-5 activate all cells in the body. (brinda.info)
  • Using these probes, evidence was provided that gp170/80-110 is identical with human lysosomal-associated membrane protein 2 (h-lamp-2), because both proteins were immunologically cross-reactive and screening of a cDNA expression library from human promyelocytic leukemia cells with anti-gp130 Ab yielded a clone derived from h-lamp-2. (rupress.org)
  • By contrast, gp130 was localized in the surface membranes of endothelial cells of human glomerular and renal interstitial capillaries, rather than in lysosomes, as found for h-lamp-2. (rupress.org)
  • The effect of differential signalling by IL-6 and leukaemia inhibitory factor (LIF) which signal by gp130 homodimerisation or LIFRβ/gp130 heterodimerisation on survival and hypertrophy was studied in neonatal rat cardiomyocytes. (ox.ac.uk)
  • The LIF R alpha /gp130 receptor complex also transduces Oncostatin M signals, although LIF R alpha alone does not interact with Oncostatin M (6). (rndsystems.com)
  • The CNTF receptor is a ternary complex that contains CNTF R alpha and gp130 as well as LIF R alpha (8, 9). (rndsystems.com)
  • IL‐6 (Interleukin‐6) binds to its soluble receptor (soluble IL‐6 Receptor) and the complex then binds to gp130 149. (comprehensivephysiology.com)
  • This 55 kDa protein representing the extracellular portion of gp80 is generated by shedding, a process that seems to be controlled by protein kinase C. It is still functional, indicating that soluble gp80 plays a biological role in promoting IL-6 activity. (thermofisher.com)
  • Furthermore, soluble gp130 levels were measured in young controls (n = 200). (uni-luebeck.de)
  • LTα expression is highly inducible and when secreted, forms a soluble homotrimeric molecule. (wikidoc.org)
  • It is established that ANCA are specific for soluble enzymes of granules of polymorphonuclear neutrophil granulocytes (PMN), such as myeloperoxidase (MPO) or protease 3 (PR3). (rupress.org)
  • Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. (ajbm.net)