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

Rats were treated with alcohol either acutely (continuous, 7-hr intravenous infusion; blood alcohol levels approximately 35 mM) or chronically (liquid diet, 12-14 weeks). Three hr before killing, the animals received Gram-negative bacterial lipopolysaccharide (LPS) or saline. Hepatocytes, Kupffer cells, and liver sinusoidal endothelial cells were isolated by liver collagenase perfusion and centrifugal elutriation, and used for measurements of recombinant human [125I]interleukin-6 binding. Dissociation constant (Kd) and the amount of cell-surface receptors (Bmax) were measured on whole cells, at 4 degrees C. Two binding sites were detected on all three cell types: high-affinity (Kd1, from 20 to 125 pM) and low-affinity (Kd2, from 0.2 to 2 nM), with low Bmax (Bmax, from 0.4 to 12 fmol/10(6) cells) and high Bmax (Bmax2, from 10 to 210 fmol/10(6) cells). Hepatocytes displayed an 8-fold higher binding capacity for high-affinity sites (Bmax1) than the other two cell types. Acute ethanol treatment induced the following significant changes in the binding parameters: a decrease in Kd1 for hepatocytes and Kupffer cells, an increase in Bmax2 for hepatocytes, and a decrease in Bmax1 for Kupffer cells. Although the control (nonalcoholic) liquid diet per se completely suppressed the high-affinity binding sites, alcohol-containing diet induced only one change: a significant increase in Kd2 for hepatocytes. No changes in the binding parameters were seen after LPS administration to the chronically treated group. In the acute group, LPS mimicked alcohol action on hepatocyte binding parameters. Alcohol blunted LPS effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of acute and chronic alcohol administration to rats on the expression of interleukin-6 cell-surface receptors of hepatic parenchymal and nonparenchymal cells. 784 8

Neutralizing autoantibodies to interleukin-6 (aAb-IL-6) have been reported in healthy individuals, in patients with autoimmune diseases, and in pharmaceutically prepared pooled IgG (IVIg). We investigated the ability of aAb-IL-6 derived from IVIg to interfere with IL-6 binding to the undifferentiated monocytic cell line U-937. High-affinity aAb-IL-6, primarily of the IgG1 subclass, constituted approximately 1:10(6) of the total IgG in IVIg preparations. IL-6 binding to cellular receptors was strongly inhibited by one class of aAb-IL-6. These antibodies recognized epitope(s) on IL-6 essential for the binding of IL-6 to the alpha subunit of the IL-6 receptor (IL-6R). Another class of aAb-IL-6 recognized epitope(s) on IL-6, which is not essential for the binding to IL-6R but nevertheless important for the formation of high-affinity cellular IL-6 binding. These antibodies presumably interfered with the association of IL-6 receptor beta chains (gp130) with IL-6/IL-6R complexes, implicating that small IL-6/aAb-IL-6 immune complexes bound saturably (low affinity/high capacity) to cellular IL-6 receptors. There was no detectable binding of IL-6 through aAb-IL-6 and Fc receptors on U-937, and IVIg had no direct IL-6 receptor antagonizing activity. Dissociation kinetics of IL-6/aAb-IL-6 complexes at 37 degrees C revealed that IL-6 was liberated from 75% of the aAb-IL-6 with a half-time (t/2) approximately 4 h but bound almost irreversibly to the remaining aAb-IL-6 (t/2 > 20 h). Cellular IL-6 uptake and degradation was suppressed by aAb-IL-6. Taken together, the data suggest that loss of immunologic tolerance against IL-6 might be a novel physiological mechanism by which IL-6 activities are effectively attenuated. Finally, binding of IL-6 in complex with IgG1 aAb-IL-6 on cells expressing IL-6 receptors implicates that such cells could be targets of antibody-dependent immunological reactions, including cytotoxic reactions.
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PMID:Influence of interleukin-6 (IL-6) autoantibodies on IL-6 binding to cellular receptors. 787 95

The biological underpinnings of borderline personality disorder (BPD) and its psychopathology including states of aversive tension and dissociation is poorly understood. Our goal was to examine transcriptional changes associated with states of tension or dissociation within individual patients in a pilot study. Dissociation is not only a critical symptom of BPD but has also been associated with higher risk for self-mutilation and depression. We conducted a whole blood gene expression profile analysis using quantitative PCR in 31 female inpatients with BPD. For each individual, two samples were drawn during a state of high tension and dissociation, while two samples were drawn at non-tension states. There was no association between gene expression and tension states. However, we could show that Interleukin-6 was positively correlated to dissociation scores, whereas Guanine nucleotide-binding protein G(s) subunit alpha isoforms, Mitogen-activated protein kinase 3 and 8, Guanine nucleotide-binding protein G(i) subunit alpha-2, Beta-arrestin-1 and 2, and Cyclic AMP-responsive element-binding protein were negatively correlated to dissociation. Our data point to a potential association of dissociation levels with the expression of genes involved in immune system regulation as well as cellular signalling/second-messenger systems. Major limitations of the study are the the possibly heterogeneous cell proportions in whole blood and the heterogeneous medication.
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PMID:Gene expression profiles in relation to tension and dissociation in borderline personality disorder. 2395 Oct 8