Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Within 15 min, approximately 2.5% of 125I-labelled interleukin-6 (IL-6) injected intravenously into rats was taken up by the spleen. As determined by light microscopic autoradiography, uptake was mainly (60%) accounted for by macrophages in the red pulp. 125I-IL-6 binding in rat peritoneal macrophages was quantitatively similar to that in cultured human monocytes and T-cells. By comparison, IL-6 binding to polymorphonuclear granulocytes and freshly isolated monocytes was low. Stimulation with antigen, but not with mitogen (PWM), induced receptor presentation in B-cells, whereas antigen and mitogen downregulated the binding in T-cells. At 4 degrees C, labelled IL-6 bound to cells with a half-time of about 1.5 h. Binding appeared reversible, but dissociation was slow and incomplete. The apparent Kd for IL-6 binding was about 30 pmol l-1 in most cell types, however, values of approximately 120 pmol l-1 were obtained in polymorphonuclear granulocytes. At 37 degrees C, 125I-IL-6 was rapidly internalized by T-cells and monocyte-macrophages, and after a lag time, TCA-soluble radioactivity was released from the cells following a sigmoidal curve. Polyacrylamide gel electrophoresis of radiolabelled IL-6 cross-linked to its binding sites in T-cells, yielded receptor-ligand complexes with molar masses of 70-80 and 120-140 kg mol-1. This would agree with a dimeric conformation of the IL-6 receptor.
 ...
PMID:Cellular targets and receptors for interleukin-6. II. Characterization of IL-6 binding and receptors in peripheral blood cells and macrophages. 212 97

The interaction of recombinant human interleukin-6 (IL-6) with the soluble extracellular form of its receptor (sIL-6R) has been characterized by the application of expressions developed for quantitative affinity chromatography to results obtained with a biosensor based on surface plasmon resonance detection. First, the interaction of sIL-6R with IL-6 covalently attached to the biosensor-chip was characterized from the dependence of the surface plasmon resonance response upon the concentration of receptor injected into the biosensor. A binding constant for the interaction between sIL-6R and IL-6 was then determined from the biosensor response observed for mixtures of IL-6 and receptor--a procedure that is shown to provide unequivocal characterization of the competing reaction, irrespective of the model used to describe the biphasic interaction between partitioning receptor and immobilized IL-6. A binding constant of 5 x 10(7) M-1 has been obtained for the interaction of sIL-6R with two equivalent and independent sites on an essentially dimeric IL-6 preparation produced using the pUC vector system, and also for the interaction of sIL-6R with a monomeric IL-6 preparation that was univalent in its interaction with receptor.
 ...
PMID:Use of a biosensor with surface plasmon resonance detection for the determination of binding constants: measurement of interleukin-6 binding to the soluble interleukin-6 receptor. 789 4

Interleukin-6 (IL-6) and insulin-like growth-factor-1 (IGF-1) are cytokines produced by a variety of cells that act on a wide range of tissues, influencing cell growth and differentiation. Purified plasma membranes from human U937 monoblastic cells produced in vitro dimeric species of IL-6- and IGF-1-derived peptides through the sequential actions of surface-associated enzymes cathepsin G and transpeptidase activities. Cathepsin G degraded native unglycosylated IL-6 and IGF-1 molecules into 8-kDa and 7-kDa peptides respectively. Subsequent dimerisation of these intermediate forms into 16-kDa IL-6- and 14-kDa IGF-1-derived peptides was inhibited by acivicin and glutathione which are specific inhibitors of the standard cell-surface gamma-glutamyl transpeptidase (gamma-GT). However U937 plasma membranes, cleared of gamma-GT activity by immunoprecipitation with anti-gamma-GT and adsorption on protein-G-Sepharose, were still able to convert the intermediate forms of IL-6 and IGF-1 into dimers. Together, these observations indicate that the transpeptidase involved in the formation of the dimeric species of IL-6 and IGF-1 was related to, but distinct from, standard cell-surface gamma-GT. Cells of all hematopoietic lineages expressed gamma-GT-related activity. In contrast to the 16-kDa IL-6-derived peptide that did not retain growth-stimulating activity, the 14-kDa IGF-1 peptide was at least equipotent with native IGF-1 in the BALB/c 3T3 fibroblast DNA synthesis response. The N/O-glycosylated IL-6 was clearly as sensitive to cathepsin-G- and gamma-GT-related activities as the unglycosylated IL-6 from Escherichia coli, thus indicating that the sugar chains did not protect the cleavage sites of the two proteases on the IL-6 molecule. Our in vitro findings raise the possibility that similar proteases participate in the regulation of the catabolism of IL-6 and IGF-1 in vivo.
 ...
PMID:Protease-catalyzed conversion of insulin-like growth factor-1 and interleukin-6 into high-molecular-mass species through the sequential action of hematopoietic surface-associated cathepsin G and gamma-glutamyl transpeptidase-related activities. 791 87

Subclinical lymphocytic choriomeningitis virus infection primes mice expressing a V beta 8.1D beta 2J beta 2.3C beta 2 T cell receptor as a transgene for induction of fatal hematogenous shock after administration of a dose of staphylococcal enterotoxin B (SEB) that is tolerated by uninfected controls. The lethal effect is greatly diminished by prior depletion of the virus-primed CD4+ T cells. Evidence of transient tumor necrosis factor (TNF) secretion is detected in serum within 1 h of SEB administration, and massive amounts of interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) are present within 4-6 h. Mice are partly protected by treatment with dimeric soluble TNF receptor-Fc fusion protein or the nitric oxide synthase inhibitor, aminoguanidine, neither of which blocks SEB-induced IFN-gamma or IL-6 production. Administration of a monoclonal antibody to IFN-gamma concomitant with SEB effectively neutralizes this cytokine but has no effect on survival.
 ...
PMID:Superantigen shock in mice with an inapparent viral infection. 796 12

We describe here a novel type of synthetic peptide library, named Multimeric Synthetic Peptide Combinatorial Library (M-SPCL), where multiple small peptide ligands are tied together in the same molecule. The advantage of using small peptides in the form of M-SPCL is two-fold: first, the high density assembly of the sequences on the branching scaffold leads to signal amplification, thereby effectively lowering the binding threshold for the selection of ligands; second, to interfere with protein-protein interactions, multimericity has been shown to be a desirable feature per se. The M-SPCL is prepared by solid-phase peptide synthesis, based on the structure of Multiple Antigen Peptides. When prepared in Positional Scanning format [C. Pinilla, J. Appel, P. Blanc and R.A. Houghten. 1992. BioTechniques 13: 901-905], selection is based on the amplified interaction of a single residue in a sequence-defined position. The usefulness of the new library was demonstrated by the selection of octameric peptides, which inhibit the binding of the cytokine human interleukin-6 to its receptor, with an apparent nanomolar affinity. Tetrameric, but not dimeric, branched peptides with the same sequences were also active with comparable affinity. The success of this approach is noteworthy, since screening of the corresponding monomeric pentapeptide SPCL did not lead to the selection of any inhibitory compound in the same system.
 ...
PMID:A Multimeric Synthetic Peptide Combinatorial Library. 801 59

Determinations of total cytokine concentration in biological fluids by immunoassays face two major problems: the biochemical heterogeneity of the analyte and the interference of cytokine-binding proteins. We developed an ultrasensitive enzyme immunoassay for interleukin-6 (IL-6), using monoclonal antibodies and acetylcholinesterase as the tracer enzyme. The antibodies recognized recombinant and glycosylated forms of IL-6 equally. The antibodies measured dimeric recombinant IL-6, yet we could not detect IL-6 oligomers in plasma samples. We investigated the potential interference of soluble IL-6 receptor (sIL-6R), which is present at high concentrations in plasma samples (1 to 2 nmol/L). Heat treatment of the sample obviated the sIL-6R interference. Using calibrators in a plasma matrix, we demonstrated by fractionation, dilution, and recovery experiments that the immunoassay accurately measured total IL-6 in both normal and pathological serum and plasma samples.
 ...
PMID:Total interleukin-6 in plasma measured by immunoassay. 828 18

Since immunohistochemical studies indicated the presence of interleukin-6 in the cortices of patients with Alzheimer's disease, we were interested in the eventual biological effects of this cytokine on neuronal cells. We found that interleukin-6 and interleukin-1 induced metallothionein expression in a human neuronal (SH-SY5Y neuroblastoma) cell line. In contrast to metallothionein, amyloid precursor protein expression was unaffected by both cytokines. When searching in the same cell line for the expression of the classical 80-kDa interleukin-6 binding protein, which is part of the dimeric interleukin-6 receptor, we were unable to detect the respective mRNA. Our findings either indicate that the interleukin-6 receptor in these cells is expressed in extremely low levels or that interleukin-6 may act upon neuronal cells via a different, yet unknown neuronal receptor.
 ...
PMID:Effects of interleukin-1 and interleukin-6 on metallothionein and amyloid precursor protein expression in human neuroblastoma cells. Evidence that interleukin-6 possibly acts via a receptor different from the 80-kDa interleukin-6 receptor. 839 18

The interaction of concanavalin A with immobilized carboxylmethyldextran has been characterized by means of a biosensor based on surface plasmon resonance detection. Adsorption and desorption of this bivalent lectin to/from the biosensor surface are shown to deviate markedly from pseudo-first-order kinetics, an assumption inherent in the usual kinetic approach to the characterization of interactions by biosensor technology. Similar results for the interaction of a dimeric and hence bivalent form of human interleukin-6 with its receptor immobilized on the biosensor plate support the conclusion that this deviation from pseudo-first-order kinetics originates from multivalence of the partitioning protein. Use of the kinetic approach to characterize the binding of multivalent proteins to immobilized affinity sites on the biosensor chip is therefore precluded because of nonconformity with the model on which the quantitative analysis is based. Instead, an intrinsic binding constant of 2.5 x 10(5) M-1 for the interaction of concanavalin A with the carboxymethylated dextran layer coating the biosensor chip has been obtained by interpreting the equilibrium biosensor responses in terms of expressions developed in the context of quantitative affinity chromatography of multivalent partitioning solutes.
 ...
PMID:Effects of solute multivalence on the evaluation of binding constants by biosensor technology: studies with concanavalin A and interleukin-6 as partitioning proteins. 857 1

Recombinant human tumor necrosis factor (TNF) binding protein-1 (r-h TBP-1) and recombinant human soluble dimeric TNF receptor (rhu TNFR:Fc) were used to determine the relative contributions of TNF to phorbol myristate acetate (PMA) and cytokine-induced human immunodeficiency virus type 1 (HIV-1) replication in chronically infected cell lines. Treatment of HIV-1-infected promonocytic U1 cells with r-h-TBP-1 or rhu TNFR:Fc reduced PMA-induced HIV-1 p24 antigen production in a concentration-dependent manner, with a maximal inhibition of approximately 90%. Maximal inhibition of p24 antigen production in T-lymphocytic ACH-2 cells was 47% with r-hTBP-1 and 42% with rhu TNFR:Fc. r-hTBP-1 and rhu TNFR:Fc also decreased p24 antigen synthesized by U1 cells in response to other stimuli, including phytohemagglutinin (PHA)-induced supernatant, granulocyte-macrophage colony-stimulating factor, interleukin-6, and TNF. Addition of r-hTBP-1 to U1 cells during the last 4 h of a 24 h incubation with PMA still inhibited p24 antigen production by 15%. U1 cells stimulated with 10(-7) M PMA released approximately 1 ng/ml endogenous TBP-1 with an initial peak observed at 1 h and a second peak at 24 h after PMA stimulation. r-hTBP-1 also partially reversed inhibition of U1 cellular proliferation caused by PMA. Both r-hTBP-1 and rhu TNFR:Fc blocked PMA induction of nuclear factor (NK)- kappa B DNA-binding activity in U1 cells in association with decreases in HIV-1 replication. We conclude that soluble TNF receptors can inhibit stimuli-induced HIV-1 expression and NK- kappa B DNA-binding activity in chronically infected U1 cells.
 ...
PMID:Soluble tumor necrosis factor receptors inhibit phorbol myristate acetate and cytokine-induced HIV-1 expression chronically infected U1 cells. 860 87

gP130 transducing receptor is involved in the formation of high affinity receptors for the cytokines of the interleukin-6 (IL-6) family. Recruitment of gp130 by IL-6 associated to its receptor leads to the dimerization of the transducing component. In the present study we did characterize the B-S12 monoclonal antibody raised against gp130 and able to elicit IL-6 type biological activities. B-S12 antibody triggered strongly the proliferation of TF1 and XGI hematopoietic cell lines and was able to increase the synthesis of acute phase proteins in HepG2 hepatoma cell line. B-S12 also behaved as a synergistic factor with granulocyte-macrophage colony-stimulating factor for both proliferation and differentiation of CD34-positive hematopoietic cell progenitors. By using a symmetric enzyme-linked immunosorbent assay, allowing the detection of dimeric forms of soluble gp130, we found that addition of B-S12 to gp130 led to its dimerization. Analysis of the tyrosine phosphorylation events in gp130 and Jak kinase family members revealed that B-S12 quickly induced the phosphorylation of gp130 in a neural derived cell line, and that Jak1 and Jak2 were also recruited. In conclusion, we show that gp130 cross-linking with the B-S12 monoclonal antibody was sufficient to generate functional IL-6 type responses in hematopoietic, neural, and hepatic cells.
 ...
PMID:gp130 transducing receptor cross-linking is sufficient to induce interleukin-6 type responses. 866 9


1 2 3 Next >>