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)

Cell lines of human fibroblasts from primary cultures released reactive oxygen species, and displayed an increase in low-level chemiluminescence when stimulated with serum-treated zymosan, N-formyl-methionyl-leucyl-phenylalanine, leukotriene B4, or 12-O-tetradecanoylphorbol 13-acetate, all of which are known stimulants of respiratory burst in phagocytic cells. Non-serum-treated zymosan, interleukin-6, interleukin-2, interferon-gamma or complement factor C3b were ineffective. The primary radical species produced was O theta.2. Radical formation was continuous for up to 4 h, and it did not occur as an oxidative burst. The low level chemiluminescence probably arose from the excitation of carbonyl groups, since it remained unchanged in the presence of azide and 1,4-diazabicyclo[2.2.2]octane. While the release of reactive oxygen species in phagocytes has a function in defense mechanisms, the sustained production of such species in tissue cells may have a role in signaling mechanisms. The amounts of reactive oxygen species released by the fibroblasts upon stimulation with the stimulants mentioned above were low in comparison with the known stimulatory effects of cytokines [Meier et al. (1989) Biochem. J. 263, 539-545].
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PMID:Human fibroblasts release low amounts of reactive oxygen species in response to the potent phagocyte stimulants, serum-treated zymosan, N-formyl-methionyl-leucyl-phenylalanine, leukotriene B4 or 12-O-tetradecanoylphorbol 13-acetate. 196 84

High serum levels of endotoxin and cytokines, through which its activity is mediated, have been shown to be associated with disease severity in septic shock and in fulminant hepatic failure. In the present study, we have investigated the ability of activated charcoals (DHP-1 and Adsorba 150C) and uncharged resin (Amberlite XAD-7) to adsorb lipopolysaccharide (LPS) and various cytokines, namely tumour necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma). The capacities of the adsorbents were assessed by measurement of their equilibrium adsorption isotherms for these substances labelled with 125I. There was no single adsorbent that uniformly adsorbed LPS and the cytokines from phosphate buffered saline or human plasma. DHP-1 charcoal was superior to Adsorba 150C for all substances and was the most effective adsorbent for binding LPS, IL-1 alpha and IFN-gamma. Amberlite XAD-7 resin was most effective for TNF, IL-6 and IFN-alpha, but bound little LPS, particularly from human plasma. Ultrafiltration through a membrane which retains substances of molecular weight greater than 50 kD did not filter the cytokines from human plasma, although the molecular weight of the cytokines range from 17 to 22 kD. This demonstrated that, TNF, IL-1, IL-6, IFN-alpha and IFN-gamma readily bind to proteins and/or other large molecules in plasma.
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PMID:Removal of endotoxin and cytokines by adsorbents and the effect of plasma protein binding. 203 48

Human myelogenous leukemic cell lines (ML-1, U-937, THP-1) were induced to differentiate by treatment with various cytokines such as tumor necrosis factor, interferon-gamma and interleukin-6. However, the extent of cell maturation depended upon the types and concentrations of sera included in the culture medium. The stimulating activity of human sera on the cytokine-induced differentiation significantly exceeded that of various lots of calf serum, horse serum, fetal calf serum and fetal bovine serum, and its stimulating effects were reproducibly observed irrespective of age and sex of normal volunteers. On Sephadex G-200 gel filtration chromatography, the stimulatory substance(s) present in human sera were separated from the inhibitory substance(s) eluted near the void volume.
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PMID:Dependence of cytokine-induced human myelogenous leukemic cell differentiation on the type of serum in the medium. 211 76

The ability of a virulent strain of Mycobacterium avium to infect and replicate within human monocyte-derived macrophages of normal donors was assessed. Moreover, the ability of selected cytokines to modulate the intracellular growth of M. avium was investigated. Our virulent strain of M. avium grew progressively in human macrophages. Treatment of macrophage monolayers with interferon-gamma (IFN-gamma) did not lead to any significant change in the infection pattern. Conversely, treatment with tumour necrosis factor-alpha (TNF-alpha) led to a significant reduction in the growth of M. avium in the macrophages. In contrast, treatment of macrophages with interleukin-6 (IL-6) enhanced their susceptibility to M. avium significantly. This finding was substantiated by other results which showed that IL-6 increased the growth of M. avium in tissue culture medium. These results suggest that cytokines may influence the M. avium-macrophage interaction, in a positive or negative manner.
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PMID:Recombinant tumour necrosis factor-alpha decreases whereas recombinant interleukin-6 increases growth of a virulent strain of Mycobacterium avium in human macrophages. 212 Jan 28

Stimulated human monocytes/macrophages are a source of interleukin-6 (IL-6), which is a likely mediator involved in immune and inflammatory reactions. The means to control production of IL-6 by these cells could therefore have therapeutic applications. We report here, for lipopolysaccharide (LPS)-stimulated human monocytes in vitro, that the lymphokine, interferon-gamma (IFN-gamma) (100 U/ml), enhanced the level of IL-6 activity, whereas another lymphokine, interleukin-4 (IL-4) (greater than or equal to 0.1 U/ml; greater than or equal to 1.2 x 10(-11) M), suppressed it. The effects of the two lymphokines were manifested at the level of mRNA. The action of the IL-4 was similar to that of the glucocorticoid, dexamethasone, but observed at a lower molar concentration. Such regulation of monocyte IL-6 activity is similar to that found previously for interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) synthesis.
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PMID:Contrasting effects of interferon-gamma and interleukin-4 on the interleukin-6 activity of stimulated human monocytes. 212 Jan 29

The regulation of class I and class II HLA expression in human thyroid follicular cells was studied in vitro. Tumour necrosis factor-alpha (TNF-alpha) enhanced the expression of class I antigen on thyrocytes, but these cytokines had little effect on the expression of class II antigen. Interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) did not affect class I and class II antigen expression. The combination of interferon-gamma (IFN-gamma) with TNF-alpha or IL-1 beta enhanced the induction of class I and class II antigens, compared with the effect of IFN-gamma alone. Neither class I nor class II expression was induced by IL-6 alone or in combination with IFN-gamma. These findings suggest that TNF-alpha and IL-1 beta may have an important role in inappropriate expression of HLA antigens on thyrocytes in thyroid gland.
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PMID:Cytokine regulation of HLA on thyroid epithelial cells. 212 59

Human T cell hybridomas were constructed by somatic cell fusion in order to dissect molecular heterogeneity of human macrophage activating-factors (MAF). Two stable human hybridoma supernatants contained MAF activity capable of inducing human monocytes tumoricidal without the help of bacterial lipopolysaccharide (LPS). These supernatants in the presence of LPS could also render mouse macrophages tumoricidal. In contrast, recombinant and natural human interferon-gamma (Hu-IFN-gamma) activated human monocytes, but not mouse peritoneal macrophages. The supernatants from the two clones could neither support the growth of human-granulocyte-macrophage colony stimulating factor/human-interleukin-4-dependent (Hu-GM-CSF/Hu-IL-4) cell lines, such as AML 193 and TALL-101, nor stimulate the proliferation of human-interleukin-2-dependent human cell line and lectin-stimulated lymphoblast, which are responsive to human-interleukin-2 and human-interleukin-4. Rabbit or murine antibodies against human-interferon-gamma (Hu-IFN), human-granulocyte-macrophage colony stimulating factor, human interleukin-1 alpha, human-interleukin-1 beta, human-interleukin-6, human-tumour necrosis factor (Hu-TNF), human-lymphotoxin and human-macrophage migration inhibitory factor (Hu-MIF) could not absorb MAF activity. MAF activity in the hybridoma supernatants is associated with the two polypeptides of molecular weights of 70,000-80,000 and 20,000-30,000 daltons, as determined by gel filtration. These results indicate decisively that novel MAF molecule(s) is secreted by human T cell hybridomas.
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PMID:Constitutive production of novel macrophage-activating factor(s) by human T cell hybridomas. 212 37

Using a functioning rat thyroid cell line (FRTL-5), we examined the effects of some cytokines, particularly interleukin-1 (IL-1) on the growth of thyroid cells. In 5H medium, namely Coon's modified Ham's F-12 medium supplemented with 5% calf serum and a five-hormone preparation consisting of insulin, hydrocortisone, transferrin, glycyl-L-histidyl-L-lysine acetate and somatostatin, IL-1 enhanced the growth of FRTL-5 cells detected by [3H]TdR incorporation. However, in 6H medium (5H medium plus bovine TSH), IL-1 inhibited the growth of FRTL-5 cells. Both effects were neutralized by the addition of anti-IL-1 antibody. Furthermore, IL-1 inhibited the growth of FRTL-5 cells induced by forskolin which is known as an adenylate cyclase activator. FRTL-5 cells have specific IL-1 receptors detected by the binding of 125I-labeled IL-1 alpha. By Scatchard plot analysis, the numbers and the dissociation constants of IL-1 receptors on FRTL-5 cells were shown to be 5225/cell and 8.69 x 10(-10) M. Interleukin-2, interleukin-6 and interferon-gamma (IFN-gamma) had no significant effects on the cell growth in 6H medium, while IFN-gamma and insulin-like growth factor I stimulated cell growth somewhat in 5H medium. These results suggest that IL-1 plays a regulatory role in the growth of thyroid cells through binding to the IL-1 receptors.
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PMID:Inhibitory effect of IL-1 on the TSH dependent growth of rat thyroid cells (FRTL-5). 212 71

Affinity chromatography of crude human urinary proteins on either human recombinant interleukin-6 (rIL-6) or human recombinant interferon-gamma (rIFN-gamma) or anti IFN-gamma receptor (IFN-gamma-R) monoclonal antibodies (McAb) yielded the two respective soluble receptors in significant amounts. A single sequence of 30 amino acid residues was obtained by N-terminal microsequencing of the protein peak purified in tandem by affinity chromatography on an IL-6 column and reversed-phase high-performance liquid chromatography. This sequence was identical with the predicted N-terminal sequence of IL-6-R as previously reported. The purified IL-6-R retained its biological activity. It was used for the preparation of specific anti IL-6-R monoclonal antibodies. Analysis of the eluted proteins from both IFN-gamma and anti IFN-gamma-R columns by inhibition of solid-phase radioimmunoassay, enzyme-linked immunosorbent assay, sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blotting proved the existence of soluble IFN-gamma-R in normal urine. This finding together with the already known presence of soluble TNF receptors and a soluble IL-2 receptor found both in plasma and in urine indicates that release of soluble cytokine receptors into body fluids is a general phenomenon which occurs under normal physiological conditions.
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PMID:Purification of soluble cytokine receptors from normal human urine by ligand-affinity and immunoaffinity chromatography. 214 54

Preincubation of rat anterior pituitary (AP) cells with homologous interferon-gamma (IFN-gamma) caused a dose-dependent inhibition of ACTH secretion stimulated by CRF. The effect was seen in both monolayer and aggregate AP cell cultures and was not due to cytotoxicity. In monolayer cultures IFN-gamma also inhibited PRL and GH release stimulated by various hypothalamic releasing factors. IFN-gamma did not affect the time kinetics of the ACTH response to CRF. The dose needed for half-maximal inhibition amounted to approximately 1 (antiviral) U/ml. The effect of IFN-gamma was abrogated by an IFN-gamma-neutralizing monoclonal antibody. Furthermore, ACTH secretion by the AP cells was not affected by the anti-IFN-gamma antibody added alone, indicating that in the culture system no endogenous IFN-gamma is operational in regulating the ACTH response studied. Of the other cytokines tested [interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interferon-alpha/beta (IFN-alpha/beta)] only TNF-alpha and IL-6 were found to inhibit CRF-stimulated ACTH release, although this inhibition was less pronounced than that caused by IFN-gamma. Lipopolysaccharide, even at high doses, did not significantly inhibit the ACTH response to CRF. These results identify IFN-gamma as one of the inflammatory cytokines that, like IL-1, TNF-alpha, and IL-6, have the potential to regulate pituitary function.
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PMID:Interferon-gamma inhibits stimulated adrenocorticotropin, prolactin, and growth hormone secretion in normal rat anterior pituitary cell cultures. 216 39


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