Search results for "Interleukin-6 receptor"
showing 10 items of 17 documents
Activation of gp 130 by IL-6/soluble IL-6 receptor induces neuronal differentiation
1998
Interleukin-6 (IL-6) on target cells binds to the specific IL-6 receptor (IL-6R) and subsequently induces homodimerization of the signal-transducing protein gp130. Cells which express gp130 but no IL-6R and which therefore do not respond to IL-6 can be stimulated by the complex of IL-6 and soluble IL-6R (slL-6R). Here we show that on rat pheochromocytoma cells (PC12), the combination of IL-6 and slL-6R but not IL-6 alone induces expression of c-fos, GAP-43 and neuron-specific enolase followed by neuron-specific differentiation and formation of a neuronal network. The differentiation was dose-and time-dependent and followed the same kinetics as nerve-growth factor (NGF)-induced differentiati…
Hyper-IL-6 (H-IL-6), a Fusion Protein of Soluble IL-6 Receptor (Sil-6R), and Interleukin-6 (IL-6), Acts Synergistic with Thrombopoietin (TPO) and Ste…
1999
It has been shown that signalings from c-kit and gpl30, the signal-transducing receptor component of the IL6 receptor, act synergistic for the ex-vivo expansion of multipotential hematopoietic progenitors. A similar synergistic effect has been demonstrated for signalings from c-kit, c-mpl, and flt3. While c-kit is activated by stem cell factor (SCF), gpl30 can be activated by the complex of soluble IL-6 receptor (sIL-6R) and interleukin-6 (IL-6). Recently, a bioactive designer cytokine, H-IL-6, a fusion protein consisting of SIL-6R and IL-6 linked by a flexible peptide chain has been shown to expand human hematopoietic colony-forming cells. We tested the activity of H-IL-6 alone and in comb…
The function of the soluble IL-6 receptor in vivo.
1996
Interleukin-6 (IL-6) is considered an important mediator of acute inflammatory responses. Moreover, IL-6 functions as a differentiation and growth factor of hematopoietic precursor cells, B-cells, T-cells, keratinocytes, neuronal cells, osteoclasts and endothelial cells. IL-6 exhibits its action via a receptor complex consisting of a specific IL-6 receptor (IL-6R) and a signal-transducing subunit (gp130). Soluble forms of both receptor components are generated by shedding and are found in patients with various diseases such as AIDS, rheumatoid arthritis and others. The function of the soluble IL-6R in vivo is unknown. To discriminate between the biologic function of hIL-6 alone and that of …
The membrane distal half of gp130 is responsible for the formation of a ternary complex with IL-6 and the IL-6 receptor
1995
AbstractGp130 is the signal transducing subunit of the interleukin-6 receptor. Signaling is initiated by the complex formation of gp130 with IL-6 bound to the IL-6 receptor (IL-6R). We have subdivided the extracellular domain of gp130 in two parts and expressed the mutant proteins as soluble IgG fusion proteins in COS-7 cells. By studying the formation of the ternary complex we show that the membrane distal half of gp130 which contains a cytokine receptor domain is responsible for the interaction with the IL-6/IL-6R complex. Interestingly this is the same region which is believed to be involved in specific recognition of the related cytokines LIF, OM, and probably also of CNTF and IL-11.
Human herpes virus 8 interleukin-6 homologue triggers gp130 on neuronal and hematopoietic cells
2000
Human herpes virus-8 (HHV8) encodes a cytokine named viral interleukin-6 (vIL-6) that shares 25% amino-acid identity with its human homologue. Human IL-6 is known to be a growth and differentiation factor of lymphatic cells and plays a potential role in the pathophysiology of various lymphoproliferative diseases. vIL-6 is expressed in HHV8-associated-diseases including Kaposi's sarcoma, Body-cavity-based-lymphoma and Castleman's disease, suggesting a pathogenetic involvement in the malignant growth of B-cell associated diseases and other malignant tumours. We expressed vIL-6 in Escherichia coli as a fusion protein with recombinant periplasmic maltose binding protein. After cleavage from the…
The function of the soluble interleukin 6 (IL-6) receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL-6 and prol…
1996
Interleukin 6 (IL-6) is considered an important mediator of acute inflammatory responses. Moreover, IL-6 functions as a differentiation and growth factor of hematopoietic precursor cells, B cells, T cells, keratinocytes, neuronal cells, osteoclasts, and endothelial cells. IL-6 exhibits its action via a receptor complex consisting of a specific IL-6 receptor (IL-6R) and a signal transducing subunit (gp130). Soluble forms of both receptor components are generated by shedding and are found in patients with various diseases such as acquired immune deficiency syndrome, rheumatoid arthritis, and others. The function of the soluble (s)IL-6R in vivo is unknown. Since human (h)IL-6 acts on human and…
A novel and rapid prediction assay for the effectiveness of IL-6 receptor specific antisense oligonucleotides by proliferation inhibition of an inter…
2001
Interleukin-6 (IL-6) belongs to a family of cytokines that use receptors consisting of a common signal-transducing chain (gp130). Baf/3 cells transfected with the human IL-6 receptor (IL-6R) and gp130 (Baf/3-gp130/IL-6R) can only grow in medium containing IL-6. We attempted to interrupt the signal transducing pathway of IL-6 with the help of antisense oligonucleotides (ASOs) designed against the IL-6R. We used 18 different kinds of antisense oligonucleotides of overlapping sequences around the translational start codon of the human IL-6R. Sense ASOs were used as a control. The proliferation of cells was analysed by H-thymidine incorporation. Cell surface expression of the IL-6R was assessed…
Hepatocellular Hyperplasia, Plasmacytoma Formation, and Extramedullary Hematopoiesis in Interleukin (IL)-6/Soluble IL-6 Receptor Double-Transgenic Mi…
1998
Cytokines interact not only with membrane anchored receptors, but also with specific soluble receptors which circulate in the bloodstream. In general, soluble cytokine receptors such as soluble tumor necrosis factor receptor, soluble interleukin 1 receptor, and soluble interleukin 4 receptor compete with their membrane-bound counterparts for the ligands and therefore act as antagonists. In contrast, soluble receptors for cytokines of the interleukin-6 (IL-6) family complex with their ligands act agonistically. Interestingly, the complex of IL-6 and the soluble interleukin 6 receptor (sIL-6R) activates target cells that do not express the membrane-bound IL-6R and therefore cannot respond to …
Purification and Characterization of the Soluble Interleukin-6 Receptor from Human Plasma and Identification of An Isoform Generated through Alternat…
1996
The soluble human interleukin-6 receptor (shIL6R) was purified from human plasma. In a single immunoaffinity purification step a 140000-fold enrichment with a yield of 95% was achieved. A subsequent IL-6 affinity chromatography resulted in a homogeneous receptor preparation but only in a yield of less than 5%. The biological activity of the soluble receptor was clearly demonstrated by its ability to induce the synthesis of the acute-phase protein α1-antichymotrypsin in HepG2 cells stably transfected with IL-6. Upon gel filtration, the native shIL6R showed an apparent molecular mass of 93 kDa. Analysis by SDS/PAGE revealed an apparent molecular mass of 65 kDa for the soluble receptor. Deglyc…
Combined interleukin 6 and soluble interleukin 6 receptor accelerates murine liver regeneration.
2000
Abstract Background & Aims: Liver regeneration after loss of hepatic tissue leads to hepatocyte and nonparenchymal cell proliferation and rapid restoration of liver parenchyma. Interleukin (IL)-6 is a key inducer of transcription factors involved in liver regeneration. Whenever IL-6 activates target cells, it binds to a specific IL-6 receptor (IL-6R). The IL-6/IL-6R complex then associates with the signal transducer gp130, leading to activation of intracellular signaling. Methods: We have recently constructed the designer cytokine Hyper-IL-6 consisting of soluble IL-6R covalently linked to IL-6, which directly stimulates gp130 even in the absence of membrane-bound IL-6R. We compared the inf…