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)

We examined whether recombinant cytokines enhance the in vitro platelet production of interleukin-3 (IL-3)-induced human megakaryocytic colonies (Meg-colony). We classified Meg-colonies into four categories based on platelet production during in situ observation on day 14: type 0, absence of cytoplasmic processes in a colony; type 1, one to three processes in at least one megakaryocyte in a colony; type 2, four to eight processes; type 3, more than nine processes or division of cytoplasm. Type 3 colonies were considered to be platelet-producing. In control cultures, type 1 Meg-colonies were dominant, followed by type 2, type 3 and type 0. Of the cytokines added at the initiation of culture, interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), and granulocyte/macrophage colony stimulating factor (GM-CSF) significantly increased the number of colonies. Furthermore, these three cytokines significantly elevated the proportion of type 3 colonies. Interleukin-4 (IL-4), granulocyte-CSF, macrophage-CSF and erythropoietin did not affect the colony count or distribution of colony type. IL-1 alpha, IL-6 and GM-CSF also significantly elevated the proportion of type 3 colonies, even when added to the culture on days 8 or 11. These results indicate that IL-1 alpha, IL-6 and GM-CSF promote platelet production of in vitro Meg-colonies.
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PMID:Megakaryocyte potentiating activity of IL-1, IL-6 and GM-CSF as evaluated by their action on in vitro human megakaryocytic colonies. 191 39

We demonstrated significant titers of interleukin-6 (IL-6) in the CSF from 6 of 11 patients with HTLV-I-associated myelopathy (HAM). The patients positive for IL-6 generally had more severe clinical symptoms and signs than those negative for IL-6. There was no correlation between the value of IL-6 and inflammatory findings in the HAM CSF.
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PMID:Interleukin-6 in cerebrospinal fluid of HTLV-I-associated myelopathy. 201 Dec 62

We have undertaken cellular and biochemical examination of bronchoalveolar lavage fluid from nonallergic patients with asthma to determine the nature and degree of inflammatory process in symptomatic asthma. Six patients with asthma (mean methacholine provocative concentration causing a 20% fall in FEV1 was 0.26 mg/ml) and six control subjects underwent fiberoptic bronchoscopy with bronchoalveolar wash. The patients with asthma shed a higher number of epithelial cells into lavage fluid than normal control subjects (p less than 0.05). Their lavage fluid also contained increased numbers of neutrophils (p less than 0.025), eosinophils (p less than 0.025), and basophilic cells (p less than 0.025), and increased proportion of activated T cells (p less than 0.05). The basophilic cells were mast cells, as indicated by positive labeling with the monoclonal antibody MCG35. Biochemical analysis of lavage fluid demonstrated exudation of protein molecules in airways of patients with asthma with increased contents of albumin (p less than 0.05) and fibronectin (p less than 0.05). In the lavage fluid of patients with asthma, there were also increased amounts of interleukin-1-beta (IL-1-beta) (p less than 0.025), interleukin-6 (IL-6) (p less than 0.025), and granulocyte-macrophage, colony-stimulating factor (GM-CSF) (p less than 0.05), as compared with lavage fluid of normal control subjects. Immunocytochemical evaluation of lavage cells demonstrated that IL-1-beta, IL-6, and GM-CSF were mostly produced by nonciliated epithelial cells and/or monocytes. IL-1, IL-6, and GM-CSF can prime granulocytes to respond to other stimuli and can promote T cell activation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cellular and biochemical characteristics of bronchoalveolar lavage fluid in symptomatic nonallergic asthma. 201 75

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

To investigate possible mechanisms of growth factor expression in acute myeloid leukemia, genes for granulocyte macrophage colony-stimulating factor (GM-CSF) were analyzed by Southern blots in 20 patients, for M-CSF in 13, for interleukin-6 (IL-6) in 14, for IL-6 receptor in 14 and for G-CSF in five patients. Only in one patient a complex rearrangement of the G-CSF gene with possible amplification was noted indicating rarity of direct alterations of growth factor genes in acute myelogenous leukemia (AML). Spontaneous m-RNA expression for GM-CSF was found in only one of 20 patients, and for IL-6 in eight of 11 patients. In vitro incubation of AML cells of eight patients with recombinant tumor necrosis factor for 24 hr revealed induction of GM-CSF m-RNA expression in three cases and GM-CSF protein expression in two of them. These data suggest that spontaneous GM-CSF production occurs rarely in AML and that monokines, such as tumor necrosis factor, may induce GM-CSF in AML cells. Therefore, interactions of AML cells with normal or malignant accessory cells may be important for autocrine stimulation in AML. Our data suggest that ectopic growth factor secretion is not the primary cause of generating AML but may contribute to progression of the disease. Alternatively, AML may represent a heterogenous group of leukemias with different etiology but similar phenotype.
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PMID:Mechanisms of growth factor expression in acute myeloid leukemia (AML). 219 15

The viability of normal bone marrow myeloid precursor cells induced by interleukin-6 (IL-6) or IL-1 alpha and the ability of IL-6 and IL-1 alpha to induce the formation of colonies of granulocytes, macrophages, or megakaryocytes in densely seeded bone marrow cultures was suppressed by transforming growth factor-beta 1 (TGF-beta 1). Induction of normal bone marrow colony formation by IL-3 was much less sensitive to TGF-beta 1, and there was little or no effect of TGF-beta 1 on colony formation induced by macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage CSF (GM-CSF). In different clones of myeloid leukemic cells, TGF-beta 1 suppressed differentiation induced with IL-6, IL-1 alpha, or lipopolysaccharide (LPS), but did not suppress differentiation induced with IL-3 or GM-CSF. The effect of TGF-beta 1 on differentiation of the leukemic cells can be dissociated from its effect on cell growth. TGF-beta 1 suppressed the production of IL-6 in normal bone marrow cells cultured with IL-1 alpha and the production of IL-6 and GM-CSF in leukemic cells cultured with IL-1 alpha or LPS. The suppression of IL-6 production can explain the suppression by TGF-beta 1 of the effects of IL-1 alpha and LPS that are mediated by IL-6. TGF-beta 1 also suppressed differentiation in clones of myeloid leukemic cells induced with differentiation factor/leukemia inhibitory factor and tumor necrosis factor. In different leukemic clones TGF-beta 1 suppressed or enhanced induction of differentiation with dexamethasone. The results show that TGF-beta 1 can selectively control the activity of different molecular regulators of normal and leukemic hematopoiesis.
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PMID:Selective regulation of the activity of different hematopoietic regulatory proteins by transforming growth factor beta 1 in normal and leukemic myeloid cells. 220 8

We identified the cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF), and interleukin-6 (IL-6) by specific radioimmunoassays in the CSF of patients with multiple sclerosis (MS) and other neurologic diseases (OND). There was a high incidence of detectable IL-1 beta in patients with active MS compared with inactive MS or OND patients. TNF was also more frequently present in active MS than in OND CSF. By contrast, most MS CSF did not contain detectable IL-6. There was no correlation between the degree of CSF pleocytosis and the level of individual cytokines, suggesting that cytokine accumulations may be derived from CNS, and not CSF, cells. As IL-1 beta and TNF experimentally induce astrogliosis, demyelination, temperature elevation, lassitude, and sleep, and results raise the possibility that these cytokines may contribute to a variety of manifestations in MS and in other disease states.
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PMID:Cytokine accumulations in CSF of multiple sclerosis patients: frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6. 223 30

Purified recombinant granulocyte colony stimulating factor (G-CSF) and interleukin-6 (IL-6) stimulated the formation of similar numbers of colonies in cultures of normal mouse marrow cells. LIF and IL-6 induced comparable differentiation in clonal cultures of murine M1 leukemic cells and exhibited enhanced actions in combination. However, LIF was 16-25-fold more active than IL-6. Induction of differentiation in M1 leukemic colonies by both LIF and IL-6 was enhanced by the addition of G-CSF or M-CSF but not by GM-CSF or Multi-CSF. Both G-CSF and IL-6, but not LIF, were able to induce differentiation in murine WEHI-3B leukemic colonies, but G-CSF was 10-fold more efficient than IL-6. Both G-CSF and IL-6 were able to stimulate the proliferation of cells of the NFS-60 continuous cell line, but G-CSF was 30-fold more efficient. M1 cells constitutively produced low levels of IL-6 and production was enhanced by LIF, but the general characteristics of the actions of LIF, IL-6, and G-CSF suggested that each operates independently as a direct differentiation inducer of leukemic cells. The similarities in the biology and actions of G-CSF, LIF, and IL-6 suggest that they may be designed to exhibit coordinated biological functions in certain situations.
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PMID:Actions and interactions of G-CSF, LIF, and IL-6 on normal and leukemic murine cells. 246 11

Two cDNA clones encoding a receptor for human granulocyte-macrophage colony-stimulating factor (hGM-CSF-R) were isolated by expression screening of a library made from human placental mRNA. Pools of recombinant plasmid DNA were electroporated into COS cells which were then screened for their capacity to bind radioiodinated hGM-CSF using a sensitive microscopic autoradiographic approach. The cloned GM-CSF-R precursor is a 400 amino acid polypeptide (Mr 45,000) with a single transmembrane domain, a glycosylated extracellular domain and a short (54 amino acids) intracytoplasmic tail. It does not contain a tyrosine kinase domain nor show homology with members of the immunoglobulin super gene family, but does show some significant sequence homologies with receptors for several other haemopoietic growth factors, including those for interleukin-6, erythropoietin and interleukin-2 (beta-chain) and also to the prolactin receptor. When transfected into COS cells the cloned cDNA directed the expression of a GM-CSF-R showing a single class of affinity (KD = 2(-8) nM) and specificity for human GM-CSF but not interleukin-3. Messenger RNA coding for this receptor was detected in a variety of haemopoietic cells known to display hGM-CSF binding, and cross-linking experiments revealed a similar size for the glycosylated receptors in transfected COS and haemopoietic cells.
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PMID:Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor. 255 71

Recombinant human (rh) interleukin-6 (IL-6), in a dose range of 1 to 10 U/mL, was able to induce a low number of neutrophilic-granulocytic colonies in a CFU-GM clonogenic assay, using T cells and adherent cells, depleted low density marrow cells. A synergistic increase in the number of granulocytic colonies was observed when rhGM-CSF at suboptimal doses and IL-6 at effective doses were both present in the assay; the increase was only additive when either rhIL-1 alpha or rhIL-3 was used together with IL-6. To determine whether the increase in colony number reflects the interactions of these factors on the same hematopoietic progenitor target cells or, instead, represents activation of accessory cells, we analyzed the effect of IL-6 on the proliferation and differentiation of three growth factor-dependent leukemic cell lines that respond with continuous proliferation to the presence of GM-CSF and IL-3 in culture. One of the three cell lines (AML-193) showed limited proliferation in the presence of IL-6 followed by terminal differentiation after 14 days into basophilic-granulocytic-like cells. A synergistic proliferative response was observed on the same cells treated with both GM-CSF and IL-6. These data support the hypothesis that IL-6 may have a direct effect on myeloid hematopoietic progenitor cells, and that GM-CSF interacts synergistically with IL-6 by acting on the same target cells.
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PMID:Human interleukin-6 supports granulocytic differentiation of hematopoietic progenitor cells and acts synergistically with GM-CSF. 264 83


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