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)

Interleukin-6 (IL-6) is known to be an important modulator of acute phase (AP) protein expression in hepatocytes both in vivo and in vitro. In the present study the inducing activity of IL-6 on the expression of the AP protein haptoglobin (HP) by the human hepatoma cell line HepG2, has been evaluated. HP mRNA inducibility was analysed by Northern and slot-blot hybridization, while HP protein was detected by means of an ELISA procedure. A dose-response relationship from 0.3 to 4.8 ng/ml of a human recombinant IL-6 preparation derived from a Chinese hamster ovary (CHO) cell line was observed after 48 h of treatment. Comparable results were obtained by analysing both HP mRNA expression and HP protein secretion. Detectable induction of HP protein secretion was observed with as little as 25 pg/ml of IL-6. The effect of IL-6 was potentiated by dexamethasone, while an inhibition on HP mRNA inducibility could be prevented by lowering the foetal calf serum (FCS) concentration to 1%. Preliminary data indicate that neither IL-1 beta nor TNF-alpha were able to induce significantly HP mRNA expression and protein secretion. The activity ratio between two IL-6 preparations (from CHO and E. coli cells) obtained with a conventional IL-6 bioassay (i.e., T1165 cell growth assay) was comparable to that obtained in the induction of HP expression. The nominal specific activity of the CHO-derived IL-6 was two to three times higher with both responses.
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PMID:Determination of haptoglobin expression in IL-6 treated HepG2 cells by ELISA and by RNA hybridization--evaluation of a quantitative method to measure IL-6. 819 87

The role of tumor necrosis factor (TNF-alpha) in physiological and pathological reactions has resulted in a progressive increase of expensive TNF-alpha consumption for laboratory and clinical purposes. Following this trend, the first chemical synthesis of the gene for rHuTNF-alpha gene in Poland and its subsequent successful expression in E. coli was recently reported. In the present paper, we verify the in vitro biological activities of this TNF-alpha preparation (CMMS/TNF-alpha) in comparison with a commercially available preparation of TNF-alpha. We demonstrate that our TNF-alpha possesses strong cytotoxic activity against WEHI 164 (clone 13) cells, binds the p55 and p75 TNF receptors on cell lines, induces intercellular adhesion molecule-1 (ICAM-1) expression, and interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) release from human umbilical vein endothelial cells (HUVEC). We demonstrate its usefulness for further investigations as an effective reagent for in vitro assays.
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PMID:Comparison of the functional activities of two different preparations of human recombinant tumor necrosis factor alpha. 823 21

Infectious reactions are known to comprise changes in vasopermeability and inflammatory mediators. We used peritonitis that complicated continuous ambulatory peritoneal dialysis (CAPD) as an in vivo inflammation model to study the time courses of peritoneal permeability characteristics and mediators in dialysate. Sixteen episodes of peritonitis were prospectively followed on eight consecutive days from the onset of the infection and once after recovery (control). Dialysate night dwells were examined for marker proteins of peritoneal permeability, cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6] and prostaglandins (PGE2, 6-keto-PGF1 alpha, and thromboxane B2 [TxB2]). The clearance of beta 2-microglobulin was used as indicator of the effective peritoneal surface area. The intrinsic permeability was characterized functionally by the peritoneal restriction coefficient. All protein clearances were increased during the acute phase of peritonitis and subsequently decreased to control. Likewise, the intrinsic peritoneal permeability was elevated, as demonstrated by a decrease of the peritoneal restriction coefficient. Peritoneal appearance rates of TNF-alpha, IL-6, and prostaglandins were also increased during the acute phase. Peak values were reached on day 1. The largest increase was observed for IL-6 (median 854-fold), followed by TNF-alpha (35-fold). The vasodilating PGE2 and 6-keto-PGF1 alpha were increased 12-fold and the vasoconstricting TxB2 was increased threefold. Evidence was obtained for local intraperitoneal synthesis of IL-6 and prostaglandins. TNF-alpha production appeared to be present only during the early acute inflammatory response. Analysis of variance for repeated measurements revealed that changes in the clearance of beta 2-microglobulin were related to those in IL-6 and marginally also to TNF-alpha in dialysate. Changes in the peritoneal restriction coefficient were also related to IL-6, but were more closely related to alterations in dialysate PGE2. These findings suggest that TNF-alpha, IL-6, and PGE2 are involved in the changes in permeability characteristics during CAPD-related peritonitis.
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PMID:Relationship of TNF-alpha, interleukin-6, and prostaglandins to peritoneal permeability for macromolecules during longitudinal follow-up of peritonitis in continuous ambulatory peritoneal dialysis. 824 82

Human melanoma cell line A375 is extremely sensitive to growth inhibitory effects of oncostatin M (OM). A375 cells resistant to the antiproliferative effect of OM were isolated by exposing OM-sensitive cells to ethyl methane sulfonate (EMS) for 24 h followed by continuous exposure to OM. An A375 subline resistant to OM-induced growth inhibition was selected by a limiting dilution technique and designated 4-1.10". The resistant cells were completely refractory to OM even up to a concentration of 500 ng/ml. Interestingly, the resistant cells were also nonresponsive to the growth inhibitory effects of interleukin-6 (IL-6). Other cytokines such as transforming growth factor beta (TGF-beta), interleukin-1 (IL-1), and tumor necrosis factor alpha and beta (TNF-alpha and TNF-beta) exhibited similar growth inhibitory effects on OM-sensitive or -resistant cells. OM-resistant cells were found to possess approximately 20% of OM receptors with the same affinities as compared to the parental OM-sensitive cells. However, the affinities and number of receptors for IL-6 were the same on both cell types. The OM treatment did not alter the cyclic AMP (cAMP) level of either the parental or the resistant cells. The OM-resistant cell line will be very useful in elucidating the mechanism of OM-elicited growth inhibition.
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PMID:Selection and characterization of a variant of human melanoma cell line, A375 resistant to growth inhibitory effects of oncostatin M (OM): coresistant to interleukin 6 (IL-6). 827 94

Immunocytochemical staining of spinal cords from five autopsied patients with HTLV-I-associated myelopathy/tropical spastic paraparesis was performed using a panel of monoclonal or polyclonal antibodies reactive with interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, interferon (IFN)-alpha, IFN-beta, IFN-gamma and transforming growth factor (TGF)-beta. In the spinal cords of patients with a shorter duration of illness, IL-1 beta, TNF-alpha, and IFN-gamma were expressed on perivascular infiltrating macrophages, astrocytes and microglia in active-chronic inflammatory lesions. In striking contrast, we rarely noted cytokine expression except for IFN-gamma in inactive-chronic lesions of patients with longer durations. In situ expression of these cytokines on microglia and astrocytes, in addition to infiltrating mononuclear cells, suggests that glial cells participate in the inflammatory process, especially in active lesions. In addition, the cytokine expression was gradually downregulated along with duration of illness.
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PMID:Cytokine expression in the spinal cord lesions in HTLV-I-associated myelopathy. 830 22

Although plasma levels of tumor necrosis factor (TNF) are elevated and hepatocellular dysfunction occurs even in the early hyperdynamic stage of sepsis, the precise mechanism responsible for this dysfunction remains unknown. Although TNF at high doses produces circulatory failure, it is not known whether the dose of TNF that does not adversely affect hemodynamics alters hepatocellular function. To study this, recombinant murine TNF-alpha was infused intravenously (0.05 or 0.25 mg/kg) over 30 min in normal rats. At 1 and 4 h after infusion of TNF-alpha or an equivalent volume of saline, hepatocellular function [i.e., maximum velocity (Vmax) and Michaelis constant (Km)] was assessed using in vivo indocyanine green clearance without blood sampling. Additional parameters measured were as follows: cardiac output by dye dilution, hepatic microcirculation by laser Doppler flowmetry and colloidal carbon infusion, plasma TNF and interleukin-6 (IL-6) by cytokine-dependent cellular assays, and plasma glucose enzymatically. The results indicate that although infusion of 0.05 mg/kg TNF-alpha did not affect Vmax and Km, its infusion at 0.25 mg/kg produced a significant depression of hepatocellular function and markedly increased the synthesis and/or release of IL-6. TNF-alpha-induced hepatocellular dysfunction was not associated with any significant changes in hepatic microcirculation, plasma glucose, cardiac output, and other measured hemodynamic parameters. Thus hepatocellular dysfunction observed after TNF infusion may be due to the direct effect of this cytokine alone or in combination with IL-6.
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PMID:Tumor necrosis factor-alpha produces hepatocellular dysfunction despite normal cardiac output and hepatic microcirculation. 820 42

Lipopolysaccharide treatment of mouse macrophage-like J774 cells was found to result in the activation of three different nuclear proteins which specifically bind to oligonucleotide containing the NF-kappa B motif of the human immunodeficiency virus (HIV) gene. These are designated as NF-kappa B1, -kappa B2, and -kappa B3, according to their electrophoretic mobilities (fast, intermediate, and slow, respectively). Immunological and UV cross-linking studies showed that NF-kappa B1 consists of only p50 subunit, whereas both NF-kappa B2 and -kappa B3 contain NF-kappa B p65 subunit and c-Rel. In addition, NF-kappa B2 was also found to contain p50 subunit of NF-kappa B. The binding of three types of NF-kappa B proteins to HIV NF-kappa B motif was effectively inhibited by other NF-kappa B motifs, whose 3' half-site nucleotide sequences are T/A-T-T/C-CC (HIV, interleukin-6, interferon (INF)-beta, H2-Kb, I-E alpha d, and TNF-alpha 2 (nucleotide position -510)) and much less effectively by NF-kappa B motifs with 3' half-site sequences of TGCCC (TNF-alpha 3, nucleotide position -610), ATCTC (G-CSF), TATTC (Fc gamma R), or TCCTT (TNF-alpha 1, nucleotide position -850). Our data also suggested that NF-kappa B1 and -kappa B2 which contain p50 subunit of NF-kappa B bind with the higher preference for NF-kappa B motif of H2-Kb gene promoter than that of INF-beta, whereas NF-kappa B3 which does not contain p50 subunit appears to preferentially bind to NF-kappa B sites of IFN-beta.
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PMID:Influence of 3' half-site sequence of NF-kappa B motifs on the binding of lipopolysaccharide-activatable macrophage NF-kappa B proteins. 836 97

Tumor necrosis factor (TNF-alpha) acts as a growth stimulatory factor on leukemic B lymphocytes from many patients with chronic lymphocytic leukemia (CLL). Because TNF induces production of interleukin-6 (IL-6), which has been shown to be a growth factor for myeloma and other transformed B cells, we examined the possibility that IL-6 mediates the growth-stimulatory effect of TNF on B-CLL cells. In fact, we found that IL-6 is an inhibitor of B-CLL growth. The addition of recombinant human IL-6 markedly decreased the TNF-induced B-CLL growth, and this decrease was even greater when soluble IL-6 receptor, known to act as IL-6 agonist, was added with recombinant IL-6. Conversely, neutralizing monoclonal antibodies to IL-6 and to the IL-6 receptor potentiated the growth stimulation of TNF on B-CLL cells, in line with the possibility that IL-6 functions as a negative feedback regulator of an autocrine TNF action on these B-leukemic cells. Evidence is presented that production of IL-6 by monocytes and B cells of CLL patients is low, suggesting that administration of IL-6 may be beneficial in CLL to reduce the eventual growth stimulation by TNF and, possibly, also the deficiency in platelets and Ig production in this disease.
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PMID:Interleukin-6 inhibits the proliferation of B-chronic lymphocytic leukemia cells that is induced by tumor necrosis factor-alpha or -beta. 838 26

The trophoblast, an epithelial cell of fetal origin that forms the physical barrier between the mother and developing conceptus, becomes a component of the host immune system during pregnancy. Of the classical immune cells, it most closely resembles the macrophage, also present in high numbers in the pregnant uterus. The macrophage and trophoblast, as cell classes, share characteristics such as phagocytosis, syncytialization, invasiveness, expression of the proteins CD4, CD14, IgG receptor (FcR), non-specific esterase, granulocyte macrophage-CSF (GM-CSF), colony stimulating factor 1 (CSF-1), interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor (TNF-alpha), transforming growth factors (TGF), platelet-alpha derived growth factor (PDGF) and receptors for these cytokines. In the uterus both cell types appear regulated by a common element, the uterine epithelium, that secretes cytokines such as CSF-1, GM-CSF, TNF alpha, TGF beta, IL-6, and leukaemia inhibitory factor (LIF) that target both macrophages and trophoblasts. The common characteristics and regulation that make teleological sense in terms of co-ordinating local uterine immunity during pregnancy may also be important in transmission of congenital diseases such as AIDS. The production by the uterine epithelium of a number of cytokines previously only associated with mononuclear phagocyte production and function predicts the existence of a similar, but broader, shared cytokine network encompassing trophoblast and the principal immune regulatory cell, the T lymphocyte.
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PMID:The trophoblast as an integral component of a macrophage-cytokine network. 843 11

We have recently described a murine model of Staphylococcus aureus-induced septic arthritis. One of the hallmarks of this disease is a striking hypergammaglobulinemia. In the present study we have used a sensitive ELISPOT technique to assess, at the single cell level, the B-cell differentiation properties of this arthritogenic, toxic shock syndrome toxin-1 (TSST-1)-producing staphylococcal strain. In vivo, inoculation of live S. aureus resulted in lymphoproliferation, early (within 3-4 days) peak of IgM-secreting cells and late (2 weeks after the injection) pronounced increase of IgG-secreting cells. We have documented that this late increase of IgG-secreting cells is a CD4+ T-cell-dependent phenomenon. Furthermore, we have showed that there is a relationship between the hypergammaglobulinemia and the appearance of arthritis, since a nonarthritogenic staphylococcal strain will not give rise to increased frequency of immunoglobulin-secreting cells. To elucidate mechanisms responsible for S. aureus-induced polyclonal B-cell activation, we have assessed in vitro effects of formalin-fixed arthritogenic S. aureus on the release of cytokines. Our results show that the S. aureus LS-1 strain induces in vitro preferentially IgM-secreting cells, many of them displaying autoantibody properties. The magnitude of this response is high and comparable with optimal concentrations of LPS, a potent murine polyclonal B-cell activator. Interleukin-1 alpha (IL-1 alpha), tumor necrosis factor (TNF), and interleukin-6 (IL-6) were all secreted by mouse MNC after in vitro exposure to formalin-killed S. aureus. Inhibition experiments, using neutralizing antibodies to these cytokines, revealed that IL-1 alpha and IL-6 but not TNF-alpha had potent B-cell differentiation properties in S. aureus-stimulated cell cultures.
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PMID:Polyclonal B-cell activation by an arthritogenic Staphylococcus aureus strain: contribution of T-cells and monokines. 845 72


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