UNIPROT:P04141 - FACTA Search

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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies in recent years have suggested that human tumor cell lines are capable of responding in vitro to hematopoietic growth factors. In the present study, we investigate the transcription of the alpha and beta subunits of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor, the alpha and beta subunits of interleukin 3 (IL-3) receptor, and the single subunit of interleukin 6 (IL-6) receptor and its associated gp130 transduction protein by PCR amplification of reverse-transcribed cellular mRNA in 34 malignant cell lines derived from a variety of histological cell types. mRNA for only a single subunit polypeptide was found in a significant minority of cell lines (23%), while in 20% both the alpha and beta subunits of either the GM-CSF receptor or the IL-3 receptor were detected among a number of different histological cell types. Transcription of the gene encoding the IL-6 receptor was found in 38% of cell lines, and all lines transcribed the gp130 transduction protein, consistent with previous observations on the ubiquity of that polypeptide. In order to test the in vitro effect of exogenously added growth factors on those malignant cell lines transcribing complete cytokine receptor, either GM-CSF, IL-3, or IL-6 was added in therapeutic concentrations (20-500 ng/ml) and cellular proliferation was measured by incorporation of [3H]thymidine. No stimulation was seen at either 3 and 6 days of culture. Production of cytokine by these cell lines was investigated at the level of transcription and by assay of peptide product. None transcribed mRNA for either GM-CSF or IL-3, while 5 of 6 (STD, DOZ, ADE, Hep-2, and Detroit) expressed IL-6 mRNA. Of these latter, 2 cell lines (ADE and Hep-2) produced IL-6 as determined by bioassay, while none produced GM-CSF or IL-3 by enzyme-linked immunosorbent assay. This suggests that in the case of GM-CSF and IL-3, failure to proliferate on addition of cytokine is not due to the prior presence of endogenous production. In contrast, at least a subset of malignant cell lines may involve a closed IL-6 autocrine loop saturating cell surface sites. These findings suggest that the ability to transcribe the genes encoding cytokine receptor is by itself insufficient to render cells cytokine responsive and that malignant cells may lack the cellular machinery for cytokine-induced proliferation. This in turn suggests that therapeutic administration of either GM-CSF, IL-3, or IL-6 may involve no additional risk of tumor regrowth in vivo.
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PMID:Transcription of genes encoding granulocyte-macrophage colony-stimulating factor, interleukin 3, and interleukin 6 receptors and lack of proliferative response to exogenous cytokines in nonhematopoietic human malignant cell lines. 831 22

We analyzed the effect of several growth factors and cytokines on the expression of amyloid beta protein precursor (APP) mRNAs in cultured mouse neuronal and glial cells. In neuronal cultures from embryonic day-15 brain. Northern blotting revealed that APP mRNAs increased by 1.3- to 2.6-fold when treated with nerve growth factor, basic fibroblast growth factor, interleukin 1, interleukin 2, interleukin 3, interleukin 6 or granulocyte-macrophage colony-stimulating factor but not with tumor necrosis factor alpha. An S1 nuclease protection assay revealed that the enhanced APP mRNA in neuronal cultures was exclusively APP695 mRNA. On the other hand, astrocyte-enriched cultures prepared from postnatal day-2 brain did not show any significant alteration among these factors. We conclude that certain growth factors and cytokines could enhance APP 695 mRNA expression in neurons in vitro.
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PMID:Effect of growth factors and cytokines on expression of amyloid beta protein precursor mRNAs in cultured neural cells. 847 81

Interleukin 6 is a 184-aa polypeptide postulated to belong to the class of helical cytokines. We built a three-dimensional model of human interleukin 6 based on the similarity of its hydrophobicity pattern with that of other cytokines and on the x-ray structure of growth hormone, interleukin 2, interleukin 4, interferon beta, and granulocyte-macrophage colony-stimulating factor. The resulting model is a bundle of four alpha-helices and suggests possible alternative conformations for the 9 C-terminal amino acids; in this region, the importance of Arg-182 and Met-184 for biological activity has been demonstrated [Lutticken, C., Kruttgen, A., Moller, C., Heinrich, P.C. & Rose-John, S. (1991) FEBS Lett. 282, 265-267]. Therefore, we generated a large collection of single-amino acid variants in residues 175-181. Analysis of their biological activity in two systems and the receptor binding properties of a subset of the mutants indicates that the entire region is involved in forming the receptor binding surface and supports the hypothesis that this region does not assume an alpha-helical conformation. Remarkably, we also found a mutant with receptor affinity and biological activity much higher than wild type; the potential therapeutical value of this finding is discussed.
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PMID:Saturation mutagenesis of the human interleukin 6 receptor-binding site: implications for its three-dimensional structure. 848 22

The presence and concentration of selected cytokines (interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated in the sera of 12 burned patients (6-90 per cent body surface area). The presence of cytokines in the sera of 20 healthy volunteers (control group) was always undetectable (< 2 pg/ml). In sera of the burned patients the concentrations of IL-4 or GM-CSF were also below the test sensitivity levels, while G-CSF and IL-6 were present throughout all the observation period and IL-8 was detectable at the onset of massive infections. The serum concentrations of G-CSF and IL-6 increased during the episodes of clinically and bacteriologically detectable infections. Their increases were, however, observable 12-24 h later than the other infection symptoms. Similar increases in G-CSF and IL-6 levels have been detected during corrective surgery (covering of granulation tissue with skin grafts). It may be concluded that serum G-CSF and IL-6 levels in burned patients may be considered as diagnostic factors, but the delays in the reaction to the massive infection do not allow us to use them for predicting the time of onset of the infection.
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PMID:Serum cytokine levels (IL-4, IL-6, IL-8, G-CSF, GM-CSF) in burned patients. 855 85

The in vitro effects of interleukin 1 (IL1) secreted by acute myelogenous leukemia (AML) blasts (termed endogenous IL 1 secretion) were investigated. Interleukin 1-dependent AML blast functions were inhibited during in vitro culture either by IL1-specific neutralizing antibodies (anti-IL1 alpha and anti-IL1 beta) or by the IL1 receptor antagonist (IL1RA). Endogenous IL1 secretion showed a wide variation between individual patients, but despite this variation IL1 inhibition significantly decreased both spontaneous blast proliferation and spontaneous blast secretion of IL1 alpha, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha and interleukin 6. In contrast to spontaneous blast proliferation, in the presence of exogenous hematopoietic growth factors (granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin 3, tumor necrosis factor alpha, stem cell factor), IL1 inhibition caused either increased or decreased AML blast proliferation depending on the individual patient. When AML blasts were cultured with stem cell factor plus granulocyte-macrophage colony-stimulating factor, IL1 inhibition significantly increased AML blast proliferation. Thus, IL1 is important for regulation of AML blast proliferation and cytokine secretion independent of the level of endogenous IL1 secretion, but the final effect of IL1 is highly dependent on the cytokine network in the AML blast microenvironment.
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PMID:Effects of endogenous interleukin 1 on blast cells derived from acute myelogenous leukemia patients. 863 79

Blast cells derived from peripheral blood of patients with acute myelogenous leukaemia (AML) were cultured in vitro and interleukin 1 receptor antagonist (IL1RA) concentrations determined in culture supernatants. AML blasts derived from patients classified as AML-M4 and AML-M5 subtype showed an increased release of IL1RA. IL1 alpha and IL1 beta caused a similar increase in AML blast release of IL1RA, and addition of anti-IL1 antibodies decreased IL1RA release. IL1RA release from AML blasts was also increased by stem cell factor, tumour necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor, whereas interleukin 3, interleukin 6, leukaemia inhibitory factor and granulocyte colony-stimulating factor did not significantly alter IL1RA release. When investigating IL1RA serum levels, serum concentrations were decreased in acute leukaemia patients with chemotherapy-induced cytopenia compared with healthy controls. Serum levels of both IL1RA as well as IL1 beta and soluble TNF alpha receptors increased when the leucopenic patients developed complicating bacterial infections.
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PMID:Interleukin 1 receptor antagonist (IL1RA) in acute leukaemia: IL1RA is both secreted spontaneously by myelogenous leukaemia blasts and is a part of the acute phase reaction in patients with chemotherapy-induced leucopenia. 869 37

Apoptosis induced by wild-type p53 or cytotoxic compounds in myeloid leukemic cells can be inhibited by the cytokines interleukin 6, interleukin 3, granulocyte-macrophage colony-stimulating factor, and interferon gamma and by antioxidants. The antioxidants and cytokines showed a cooperative protective effect against induction of apoptosis. Cells with a higher intrinsic level of peroxide production showed a higher sensitivity to induction of apoptosis and required a higher cytokine concentration to inhibit apoptosis. Decreasing the intrinsic oxidative stress in cells by antioxidants thus inhibited apoptosis, whereas increasing this intrinsic stress by adding H2O2 enhanced apoptosis. Induction of apoptosis by wild-type p53 was not preceded by increased peroxide production or lipid peroxidation and the protective effect of cytokines was not associated with a decrease in these properties. The results indicate that the intrinsic degree of oxidative stress can regulate cell susceptibility to wild-type p53-dependent and p53-independent induction of apoptosis and the ability of cytokines to protect cells against apoptosis.
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PMID:Cellular oxidative stress and the control of apoptosis by wild-type p53, cytotoxic compounds, and cytokines. 879 72

The course of hairy cell leukemia (HCL) is characterized by progressive pancytopenia. The pathogenesis of this phenomenon is still not fully understood. To study if the decrease in hematopoiesis in HCL is accompanied by abnormal concentrations of growth factors, we investigated the production of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin 3 (IL-3), interleukin 6 (IL-6), and tumor necrosis factor alpha by peripheral blood mononuclear cells (PBMCs) of eight patients with HCL. The results point to a severe deficiency of production of all cytokines tested as compared to healthy donors. However, enrichment of autologous monocytes by counterflow centrifugation resulted in a marked increase of the levels of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, IL-6, and tumor necrosis factor alpha. The most pronounced effects were seen with IL-6. Reverse transcription-PCR analysis indicated that pokeweed mitogen, IFN-alpha, and poly(I:C) are capable of inducing the expression of IL-6-specific mRNA in HCL cells. These findings are substantiated on the protein level by immunofluorescence analysis. Incubation of PBMCs with IFN-alpha resulted in a significant increase of intracellular IL-6 in HCL but not in healthy donors. This increase was also seen in hairy cells positive for CD19 and CDllc. Furthermore, IFN-alpha induced the secretion of IL-6 from PBMCs of HCL patients but not healthy donors. In conclusion, our studies with PBMCs from patients with HCL revealed an inadequate supply of hematopoietic growth factors that might, in part, be due to the monocytopenia characteristic for this disease. The findings also indicate that IFN-alpha is capable of inducing the production of IL-6 in the patients' PBMCs as well as in their hairy cells. These data from our in vitro studies support the clinical observation that treatment with IFN-alpha leads to reconstitution of hematopoiesis.
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PMID:Inadequate production of hematopoietic growth factors in hairy cell leukemia: up-regulation of interleukin 6 by recombinant IFN-alpha in vitro. 884 Sep 84

Patients infected with human immunodeficiency virus (HIV) frequently have increased production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and these cytokines may in turn contribute to the disease pathogenesis. It has been hypothesized that secretion of these cytokines by HIV-exposed mononuclear cells or HIV-infected monocyte/macrophages (M/Ms) is the principal source of their overproduction in HIV-infected patients, and the present study was undertaken to explore this issue. We observed that in the absence of endotoxin or cytokines, M/Ms productively infected by HIV do not produce detectable IL-6 or TNF-alpha. However, granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that enhances HIV replication in M/Ms and is frequently used to propagate monocytotropic strains of HIV, can induce the relatively long-term production of IL-6 (up to 47 U/ml) and TNF-alpha (up to 47 pg/ml) by M/Ms, even in the absence of HIV. Also, HIV induced production of a relatively small (< or = 9 U/ml) quantity of IL-6 in M/Ms stimulated with macrophage-colony stimulating factor (M-CSF). Finally, while highly concentrated HIV induced production of both cytokines by either M/Ms or peripheral blood mononuclear cells (PBMCs), this production was almost completely eliminated when care was taken to avoid contamination of HIV by endotoxin. These data suggest that the excess IL-6 and TNF-alpha in HIV-infected patients does not simply result from their production by HIV-infected M/Ms and that alternative mechanisms are involved in this process.
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PMID:Effects of human immunodeficiency virus and colony-stimulating factors on the production of interleukin 6 and tumor necrosis factor alpha by monocyte/macrophages. 919 77

Bladder cancer cells have been shown to secrete a variety of factors that are not related to cells of urothelial origin. The histogenesis of these tumour developments is uncertain, and a variety of theories have been previously reported. In the present manuscript, we identify the factors constitutively produced by a human bladder cancer cell line (KU-19-19) that was found to produce beta human chorionic gonadotrophin (beta-hCG), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1alpha (IL-1alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8). The cells were obtained from a case of metastatic carcinoma that was originally diagnosed to be a grade 3 (WHO classification), invasive transitional cell carcinoma of the bladder. On microscopic observation, the cultured cells exhibited an epithelial appearance with vacuole formation in their cytoplasm. Ultrastructural observations revealed relatively marked microvilli and a tight junction. Significant amounts of beta-hCG, G-CSF, GM-CSF, IL-1alpha, IL-6 and IL-8 concentrations in the supernatant from cultured cells were demonstrated by enzyme-linked immunosorbent assays, while the expression of mRNA of these marker proteins in cancer cells was also significantly exhibited by reverse transcription polymerase chain reaction (RT-PCR). In addition, the expression of G-CSF receptor and IL-6 receptor mRNA was also shown by RT-PCR. Xenograft transplantability using nude mice was observed in association with the presence of severe neutrophilia in the peripheral blood. These results indicate that this cell line appears to be an effective model for the study of transitional cell carcinoma of the bladder with multipotent differentiation potentials.
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PMID:Constitutive production of multiple cytokines and a human chorionic gonadotrophin beta-subunit by a human bladder cancer cell line (KU-19-19): possible demonstration of totipotential differentiation. 923 15

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