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-free supernatant of cultures from Mycoplasma arthritidis (MAS) functions as an extremely potent T-cell mitogen for human and murine lymphocytes. The T-cell response is dependent on the presence of accessory cells, presenting the intact E2 molecule on the cell surface. Until now, pure MAS protein has not been available. We developed a new multi-step method for MAS purification. The main steps in this protocol are ammonium sulfate precipitation, anion exchange and hydroxyapatite chromatography followed by gel filtration. With this efficient protocol we obtained fractions of extremely potent mitogenic properties, the purification rate was about 5 x 10(5). Although this protease-sensitive mitogenic activity was highly enriched, we failed to detect the protein by sensitive staining methods of SDS-PAGE. In previous studies, we showed that MAS induces the synthesis of interferon gamma in human and murine lymphocyte cultures. Here we demonstrate that MAS induces interleukin-6 (IL-6) in murine bone-marrow derived macrophage cultures. Since IL-6 is also induced by endotoxin, we used C3H/HeJ mice, which are known to be LPS-nonresponders, in all our studies.
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PMID:Induction of interleukin-6 in murine bone marrow-derived macrophages stimulated by the Mycoplasma arthritidis mitogen MAS. 171 97

A number of in vitro studies suggest an immunoregulatory role of 1 alpha,25 Dihydroxyvitamin D3 (1,25-(OH)2D3). The hormone inhibits production of interleukin-2 and immunoglobulin, and it blocks lymphocyte proliferation. Diverse effects on monocyte functions have been reported. However, immunological effects of 1,25-(OH)2D3 have not been substantiated in vivo. Six healthy male volunteers, aged 28-45 yr, were treated orally with 1,25-(OH)2D3 (tabl. Rocaltrol), 1 microgram twice daily for 7 days. Blood and urine samples were collected before and 7 days after initiation of treatment. Blood mononuclear cells from individuals treated with 1,25-(OH)2D3 showed a significantly reduced production of both interleukin-1 alpha (45%) and tumor necrosis factor-alpha (58%) (both measured by ELISA). Interleukin-6, production, measured by the B9 cell assay, was reduced in five individuals (78%), and unchanged in one. There was no effect on the release of interleukin-1 beta. There was no measurable effect on interleukin-2, interferon gamma or immunoglobulin production, or on mitogen-induced proliferation of blood mononuclear cells. Serum-osteocalcin and urine excretion of calcium were increased to 131 and 173%, respectively. The serum-calcium and serum-phosphate levels were unchanged.
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PMID:Down-regulation of monocyte functions by treatment of healthy adults with 1 alpha,25 dihydroxyvitamin D3. 178 65

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) of unknown etiology. They are characterized by an activation of intestinal mononuclear cells. Cytokines play a crucial role in the regulation of the functions of these cells. An increased synthesis of the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha), which are primarily synthesized by activated monocytes/macrophages has been described in patients with IBD. The synthesis of interleukin-2 (IL-2) and of interferon gamma (IFN gamma), which are produced by lymphocytes, on the other hand, has been found to be decreased. The published data are, however, not quite consistent. In patients with IBD there is not only a stimulation of the local cytokine production in the gut. The blood levels and the synthesis of the cytokines IL-1, IL-6 and TNF alpha by peripheral blood mononuclear cells are also increased, in particular in patients with Crohn's disease. Drugs, which are commonly used for the treatment of IBD impair the synthesis of these cytokines in monocytes/macrophages.
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PMID:Inflammatory mediators in chronic inflammatory bowel diseases. 179 95

Endothelin release from bovine endothelial cells of the aorta, pulmonary artery, and retinal microvessels was measured in response to various cytokines. Transforming growth factor beta (0.05-5 ng/ml) was found to be a potent stimulator (3-4 fold increase) of endothelin secretion in all three cell types. Tumour necrosis factor alpha (0.1-10 ng/ml) and interferon gamma (8-800 U/ml) had a small (1.5-2 fold increase) but significant effect on endothelin secretion from endothelial cells of large vessels but not the retinal microvessels. Interleukin-1 beta, Interleukin-6 and interleukin-8 at various doses did not affect endothelin secretion. These effects were observed at various time points from 6-24 hrs and indicate that of the cytokines tested, only transforming growth factor beta has a potent effect on endothelin release from endothelial cells of different organs.
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PMID:Cytokine stimulated endothelin release from endothelial cells. 190 Nov 27

It has been proposed that certain cytokines secreted by islet-infiltrating leukocytes may be involved in the pathogenesis of insulin-dependent diabetes mellitus. Since the cytotoxic actions by the cytokines may reflect interactions with islet cell types other than the beta-cell, in this work I have investigated the effects of different combinations of various cytokines on the proliferation and hormone content and secretion by a pure insulin-producing cell population, i.e., the clonal rat insulinoma cell line RINm5F. For this purpose RINm5F cells were exposed in culture for 1-2 days to interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and interferon alpha (IFN-alpha) at different concentrations. It was found that IL-1 beta markedly decreased the cellular content of insulin and secretion of the hormone into the culture medium, while causing a very slight inhibition of RINm5F cell proliferation. On the other hand, IFN-gamma and IFN-alpha both elicited marked decreases in proliferation and insulin content and secretion by the insulinoma cells. IL-6 and TNF-alpha were found not to affect these parameters. No additive or synergistic effects were observed when the cytokines were added in various combinations. There was no protection against the cytotoxicity of IL-1 beta, IFN-gamma or IFN-alpha by pre-treatment with pertussis toxin. From these findings it is concluded that the cytokines IL-1 beta, IFN-gamma and IFN-alpha act in a non-synergistic fashion in suppressing RINm5F cell proliferation and hormone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines inhibit proliferation and insulin secretion by clonal rat insulinoma cells (RINm5F) non-synergistically and in a pertussis toxin-insensitive manner. 195 44

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) exert multiple effects on the proliferation, differentiation, and function of myeloid lineage cells through their interaction with specific cell-surface receptors. There is a considerable degree of overlap in the biological effects of these two growth factors, but little is known about the mechanisms of postreceptor signal transduction. We have investigated the effects of GM-CSF and IL-3 on protein tyrosine-kinase activity in a human cell line, MO7E, which proliferates in response to either factor. Tyrosine-kinase activity was detected using immunoblotting with a monoclonal antibody (MoAb) specific for phosphotyrosine. GM-CSF and IL-3 were found to induce a nearly identical pattern of protein tyrosine phosphorylation using both one- and two-dimensional gel electrophoresis. Tyrosine phosphorylation of two cytosolic proteins in particular was increased more than 10-fold, a 93-Kd protein (pp93) and a 70-Kd protein (pp70). Tyrosine phosphorylation of pp93 and pp70 was observed within 1 minute, reached a maximum at 5 to 15 minutes, and gradually decreased thereafter. Other proteins of 150, 125, 63, 55, 42, and 36 Kd were also phosphorylated on tyrosine in response to both GM-CSF and IL-3, although to a lesser degree. Tyrosine phosphorylation was dependent on the concentration of GM-CSF over the range of 0.1 to 10 ng/mL and on IL-3 over the range of 1 to 30 ng/mL. Stimulation of MO7E cells with 12-0-tetradecanoyl-phorbol-13-acetate (TPA) or cytokines such as G-CSF, M-CSF, interleukin-1 (IL-1), interleukin-4 (IL-4), interleukin-6 (IL-6), interferon gamma, tumor necrosis factor (TNF), or transforming growth factor-beta (TGF-beta) did not induce tyrosine phosphorylation of pp93 or pp70, suggesting that these two phosphoproteins are specific for GM-CSF-or IL-3-induced activation. The extent and duration of phosphorylation of all the substrates were increased by pretreatment of cells with vanadate, an inhibitor of protein-tyrosine phosphatases. Importantly, culture of MO7E cells with vanadate (up to 10 mumol/L) resulted in a dose-dependent increase in GM-CSF-or IL-3-induced proliferation of up to 1.8-fold. These results suggest that tyrosine phosphorylation may be important for GM-CSF and IL-3 receptor-mediated signal transduction and that cell proliferation may be, at least partially, regulated by a balance between CSF-induced protein-tyrosine kinase activity and protein-tyrosine phosphatase activity.
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PMID:Signal transduction of the human granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors involves tyrosine phosphorylation of a common set of cytoplasmic proteins. 216 6

The effect of recombinant (r) interleukin-1 beta (rIL-1 beta) and transforming growth factor-beta (TGF-beta) on the production of interleukin-2 (IL-2) and interleukin-6 (IL-6) from an antigen-specific (LBRM-33-1A5) and an antigen-nonspecific (EL-4-NOB-1) T-cell line was investigated. rIL-1 beta induced the production of IL-2 and IL-6 from EL-4-NOB-1 cells in a dose-related manner. The LBRM-33-1A5 cells required phytohemagglutinin (PHA) in addition to rIL-1 beta in order to produce IL-2 and IL-6. IL-2 production was found to precede IL-6 production in both cell lines. No IL-2 or IL-6 production was observed by adding r murine tumor necrosis factor-alpha or r murine interferon gamma to the cells. The presence of 1 ng/ml TGF-beta reduced IL-2 and IL-6 production from both T-cell lines by more than 80%. The inhibition of IL-2 and IL-6 production was still evident by a concentration as low as 10 pg/ml of TGF-beta. rIL-1 beta and PHA also stimulated murine thymocytes to produce IL-6 which was inhibited up to 85% in the presence of 1 ng/ml TGF-beta. Taken together these results suggest that TGF-beta may suppress immune responses by inhibiting the endogenous production of IL-2 and IL-6.
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PMID:Regulation of interleukin-2 and interleukin-6 production from T-cells: involvement of interleukin-1 beta and transforming growth factor-beta. 230 41

Hypergammaglobulinaemia and enhanced serum IgA levels are common in alcoholic liver cirrhosis. Interleukin-6 (IL-6), which is identical to B cell differentiation factor BSF2 and is implicated in various autoimmune diseases, has been studied in patients with alcoholic liver cirrhosis. Increased serum levels and spontaneous or induced production of IL-6 by peripheral blood monoclonal cells have been found. IL-6 production correlates closely with IgA serum levels and negatively with impaired interleukin-2 and interferon gamma production. This abnormality could be related to overproduction of immunoglobulins and immune disturbances observed in this disease.
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PMID:High interleukin-6 serum levels and increased production by leucocytes in alcoholic liver cirrhosis. Correlation with IgA serum levels and lymphokines production. 250 58

Cytokine production was studied in thyroid tissue from patients with Graves' disease, Hashimoto's thyroiditis and non-toxic goitre. The expression of interferon gamma, tumour necrosis factor alpha and beta, interleukin-1 alpha and beta, interleukin-6 and platelet-derived growth factor A chain was assessed by slot-blot analysis of the respective mRNA in freshly isolated tissue samples. All seven cytokines were detected in patients of all groups. Although the respective mRNA levels were, in general, higher in thyroid autoimmune disorders, this appeared to relate to the degree of the lymphocytic infiltration of the thyroid gland at the time of surgery. Purified thyroid follicular cells expressed high levels of interleukin-1 alpha and interleukin-6 mRNA and when established in primary culture, purified thyroid follicular cells from Graves' disease as well as non-toxic goitre produced interleukin-1 alpha and interleukin-6 bioactivity spontaneously. In the case of interleukin-1 this could be further augmented by addition of lipopolysaccharide to the thyroid follicular cell cultures. These results demonstrate that the lymphocytic infiltrate found in autoimmune and non-autoimmune thyroid disorders is associated with cytokine production. Additionally we have shown that intrathyroidal cytokine production is not restricted to thyroid-infiltrating mononuclear cells, but may also involve thyroid follicular cells both in vivo and in vitro. The cytokines produced by thyroid follicular cells may have an important role in stimulating autoantigen specific T cells in vivo as both interleukin-1 and interleukin-6 facilitate T cell activation.
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PMID:Analysis of intrathyroidal cytokine production in thyroid autoimmune disease: thyroid follicular cells produce interleukin-1 alpha and interleukin-6. 268 Jan 82

The number of cytokine molecules identified and cloned grows almost weekly. Studies using pure preparations have shown that single entities, e.g. TGF beta and IL-1 act on a wide variety of target cells whereas other cytokines, e.g. G-CSF have a more restricted target cell population. The outcome of stimulation of a cell by a cytokine depends on the target cell type, the presence of other coexisting cytokines and, as the release of cytokines may be targeted in the direction of the stimulus, the orientation of producer and target cells. These modulating phenomena may enable a small number of cytokines to specifically define a much larger number of responses, so that maximum 'value' is obtained from the successful evolution of cytokine and receptor molecules. The current nomenclature has little regard for this, the names of cytokines often deriving from the first property observed in vitro. In many cases these are not the most important properties of the molecule and can be misleading, e.g. transforming growth factor beta, which is growth inhibitory in some systems; the antiviral action of interferon gamma is relatively minor compared to its role as a macrophage activation factor; and interleukin-1 is produced by, and acts on, many cells outside the lymphohaemopoietic system. In addition, although there is often a high degree of homology, the repertoire of activities may vary between species. For example, IL-5 is a growth factor for eosinophils, both in humans and mice, however, in the mouse it also acts as a B-cell differentiation factor--a property which has been less easy to identify in human IL-5.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multifunctional cytokines in haemopoiesis. 269 46


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