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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)

The effect of parathyroid hormone (PTH) on immunoglobulin (Ig) production and proliferation in the human B-cell lines CBL, SKW, and CESS was studied. PTH inhibited Ig production from all the B-cell lines in a dose-dependent manner during 5 days of culture. As little as 0.1 ng/ml was inhibitory. PTH also inhibited Ig production from cell lines stimulated by vasoactive intestinal peptide (VIP), interleukin 2 (IL-2), and IL-6. This inhibition was not due to decreased cell growth since proliferation was not affected and cell viability was always greater than 98%. In contrast to PTH, inactivated PTH or triiodothyronine failed to affect Ig production. Inhibition by PTH was blocked by anti-PTH serum, but not by control serum. Of the various cytokines tested, IL-4 reduced the PTH-induced inhibition of Ig production, whereas other cytokines, including IL-1 beta, IL-3, IL-5, interferon alpha (IFN-alpha), IFN-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF), failed to do so. The reducing effect of IL-4 was blocked by anti-IL-4 antibody but not by control antibody. Moreover, IFN-alpha and IFN-gamma, but not GM-CSF, overcame the reducing effect of IL-4. PTH also inhibited IgG, IgM, and IgA production by tonsillar B cells stimulated with Staphylococcus aureus Cowan strain I (SAC) and IL-6 without affecting proliferation. This inhibition was blocked by anti-IL-4 antibody but not by control antibody. These results indicate that, in addition to its regulatory effect on calcium metabolism, PTH also acts as an immunoregulatory factor, and that it interacts with the cytokine, IL-4.
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PMID:Parathyroid hormone inhibits immunoglobulin production without affecting cell growth in human B cells. 145 31

The effect of nerve growth factor (NGF) on human IgG4 production was studied. NGF specifically enhanced IgG4 production in cultures of human tonsillar mononuclear cells without affecting production of other isotypes or other IgG subclasses. Optimal enhancement of IgG4 production by NGF required the presence of T cells. However, NGF induced significant IgG4 production by small resting B cells in the absence of T cells, and this production was enhanced by stimulation with Staphylococcus aureus Cowan strain I (SAC). In contrast to small B cells, large activated B cells produced IgG4 spontaneously; this production was enhanced by NGF. NGF also enhanced IgM and IgA production by large B cells, while production of IgG1, IgG2, IgG3 and IgE was not affected. The enhancement of IgG4 production was blocked by anti-NGF serum but not by control serum. NGF, T cells and SAC, separately or together, failed to induce IgG4 production by surface (sIgG4+)-depleted B cells. In contrast to NGF, other recombinant human cytokines including interleukin (IL) 1 beta, IL 2, IL 4, IL 5, IL 6, granulocyte-macrophage colony-stimulating factor, interferon alpha and gamma failed to induce IgG4 production. These results suggest that NGF directly and preferentially stimulates activated sIgG4+ B cells to produce IgG4.
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PMID:Nerve growth factor specifically induces human IgG4 production. 199 84

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a classical haematopoietic cytokine which has been implicated in placental growth and development. In this study, we investigated the production of GM-CSF in human first trimester pregnancy by the predominant uterine lymphocyte population of decidual CD56+ NK cells (large granular lymphocytes) and the factors that influence this production using enzyme-linked immunosorbent assays (ELISAs) and bioassays, supplemented by immunocytochemistry. We have also investigated and compared production of GM-CSF by human first trimester trophoblast and by JEG-3 and JAR choriocarcinoma cells. Our data show that appreciable amounts of GM-CSF are produced in first trimester maternal decidua and that a significant component of this secretion was from decidual large granular lymphocytes (LGL). Production of GM-CSF by LGL was constitutive and considerably greater than that of freshly isolated peripheral blood leukocytes. GM-CSF secretion by decidual LGL could be enhanced by co-culture on a monolayer of decidual stromal cells, and could also be increased in a dose-dependent manner by stimulation with interleukin-1 (IL-1) or IL-2. IL-4, IL-6, tumour necrosis factor alpha (TNF alpha), transforming growth factor beta (TGF beta), interferon alpha (IFN alpha) and IFN gamma individually had no effect on GM-CSF secretion, although IL-4, TGF beta and IFN alpha all inhibited the action of IL-2. IFN gamma had no effect on the IL-2-induced GM-CSF secretion, but did antagonize the action of IL-1. Normal human first trimester trophoblast was also found to produce GM-CSF, although no production whatsoever was seen by JEG-3 or JAR choriocarcinoma cells. These results suggest that GM-CSF from uterine lymphocytes, and from trophoblast itself, may influence placental growth and development in both a paracrine and an autocrine manner.
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PMID:Production of granulocyte-macrophage colony-stimulating factor by human trophoblast cells and by decidual large granular lymphocytes. 753 Jul 25

The effect of biological response modifiers on macroscopic tumor growth and on tumor cell proliferation of a human renal cell carcinoma and a squamous cell carcinoma (hypopharynx) in nude mice has been studied. Tumor necrosis factor alpha (TNF-alpha) and interferon alpha (IFN-alpha) as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) were applied either alone or in combination, and TNF-alpha was also combined with etoposide (ETP). TNF-alpha and IFN-alpha alone or in combination did not substantially affect the course of tumor growth, however, they did influence the pattern of tumor growth. There was also only a marginal effect on tumor cell proliferation. However, IFN-alpha protects the animals from tumor growth associated weight loss. ETP and ETP plus TNF-alpha leads to a deceleration of tumor growth, a decrease of the labeling index and to a significant decrease of the animal weight which indicates that the first two effects may be partly due to the toxicity of the treatment. GM-CSF modifies cell proliferation in a dose-dependent manner, i.e. stimulation at low doses and tendency to inhibition at higher doses. Although there is no substantial direct antineoplastic effect of the agents studied, the results make clear that indirect effects of therapeutic agents due to therapy induced cachexia should always be regarded. It is interesting that IFN-alpha has a protective effect against cachexia.
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PMID:Effect of biological response modifiers on growth and cell proliferation of human tumor xenografts in nude mice. 777 38

The safety and efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjuvant therapy for interferon alpha (IFN-alpha) treatment has been evaluated in 20 non-cirrhotic patients with chronic hepatitis C virus (HCV) infection. Adjuvant therapy with GM-CSF plus IFN-alpha was associated with less myelosuppression than with IFN-alpha alone (P < .01), although the rate of local adverse reactions increased. GM-CSF adjuvant therapy led to a 50% biochemical response (transaminase values within the normal range at therapy end) and to reductions in HCV RNA concentrations (median HCV RNA reduction of 99%, range 8-100%), which were similarly observed in single IFN-alpha recipients (median HCV RNA reduction of 91%, range 38-100%). However, HCV RNA became undetectable in three biochemical responders to the GM-CSF adjuvant therapy, but in only one biochemical non-responder to IFN-alpha alone. The use of GM-CSF as adjuvant therapy is safe and, although it has not improved the biochemical response, it might potentiate the virologic response to IFN-alpha treatment alone.
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PMID:Granulocyte-macrophage colony-stimulating factor as adjuvant therapy for factor as adjuvant therapy for interferon alpha treatment of chronic hepatitis C. 916 22

Human ovarian adenocarcinoma cells N.1 secrete an autocrine activity that stimulates active cell death under serum-reduced conditions. To substitute the autocrine activity by a single physiological component, 28 cytokines, growth factors and biomodulators were tested [interleukin 1alpha (IL-1alpha), IL-1beta, IL-2, IL-3, IL-4, IL-6, IL-10, IL-11, stem cell factor (SCF), platelet-derived growth factor (PDGF), acid fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-1), IGF-2, insulin, macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), oncostatin, RANTES (regulated on activation normal T cell expressed and secreted), angiogenin, leukaemia inhibitory factor (LIF), erythropoietin (EPO), interferon alpha (INF-alpha), INF-gamma, transferrin, tumour necrosis factor alpha (TNF-alpha, TNF-beta and bovine serum albumin for control reasons]. In these experiments, only TNF-alpha and TNF-beta rapidly induced apoptosis. TNF-alpha and TNF-receptor 1 were expressed by N.1 cells, and the secretion of TNF-alpha was verified by enzyme-linked immunosorbent assay (ELISA). Autocrine factor-triggered apoptosis was inhibited when conditioned supernatant was preincubated with anti-TNF-alpha antibody. These findings suggested that the apoptosis-inducing component of the N.1 autocrine activity was TNF-alpha. In the presence of antisense c-myc oligonucleotides, induction of cell death by autocrine factor was partly inhibited. Autocrine factor and TNF-alpha stimulated transcription of the invasiveness-related protease plasminogen activator/urokinase mRNA (upa) with similar kinetics. When N.1 cells were exposed to purified plasminogen activator/urokinase protein (uPA), cell matrix contact was disrupted. Thus, uPA might serve a physiological role during TNF-induced apoptosis by affecting the interactions between cells and the basal membrane, thereby facilitating anoikis. This mechanistic study, which was restricted to a single human ovarian carcinoma model cell line (N.1), provides evidence that N.1 maintains the capacity to undergo c-myc-dependent apoptosis by the TNF-TNF-receptor pathway, and no additional pharmacological stimuli for induction of apoptosis are required.
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PMID:Autocrine self-elimination of cultured ovarian cancer cells by tumour necrosis factor alpha (TNF-alpha). 976 76

Bone marrow stroma produces positive and negative growth regulators which constitute the hematopoietic microenvironment. As many tumors metastasize to the bones, these regulators may also influence tumor growth. Hematopoietic cytokines may indeed exert both positive and negative effect on tumor growth. We report that, when mixed with tumor cells. adherent bone marrow cells inhibit primary tumor growth and metastases formation in mice transplanted with Lewis lung carcinoma or B16 melanoma. Peritoneal macrophages or lymph node cells did not exert any influence. The tumor inhibition was apparently due to soluble factor(s) released by marrow stromal cells. In cocultures with B16 melanoma cells, adherent bone marrow cells exerted a significant antiproliferative effect which was increased by previous culture of the bone marrow cells with granulocyte-macrophage colony-stimulating factor but not with macrophage colony-stimulating factor. Neither neutralizing antibodies against tumor necrosis factor-alpha, transforming growth factor-beta or interferon alpha/beta nor addition of Escherichia coli lipopolysaccharide to generate inflammatory cytokines could affect the antiproliferative effect of bone marrow stromal cells. The bone marrow stroma factor(s) which inhibit tumor growth might, therefore, be a novel growth regulator.
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PMID:Factor(s) from nonmacrophage bone marrow stromal cells inhibit Lewis lung carcinoma and B16 melanoma growth in mice. 1035 34

Sargramostim (GM-CSF) therapy was instituted in a 49-year-old woman with hepatitis C on chronic interferon alpha-2b therapy. Within two weeks, she developed progressive confusion, lethargy, and gait disturbance. At autopsy 4 months later, diffuse perivascular nonmonoclonal lymphoid infiltrates were demonstrated throughout the central nervous system (CNS). As the use of hematopoietic growth factors in clinical practice increases, potential adverse effects, such as the fulminant CNS lymphocytic proliferation in this patient, are more likely to be encountered.
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PMID:Fulminant CNS perivascular lymphocytic proliferation: association with sargramostim, a hematopoietic growth factor. 1051 80

Although interferon alpha (IFN-alpha) is able to induce haematological remission in 60-80% of patients with chronic myeloid leukaemia (CML) in early chronic phase, major cytogenetic remissions are only achievable in 30-40%. Recent clinical data suggest that the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) to IFN-alpha therapy can significantly improve the cytogenetic response in some patients, although the mechanism remains unknown. We hypothesized that the combination of GM-CSF and IFN-alpha induces the differentiation of dendritic cells, which subsequently stimulates a specific anti-leukaemic response. Monocytes from CML patients were cultured in GM-CSF and interleukin (IL)-4 (GM/IL-4)or in GM-CSF and IFN-alpha (GM/IFN-alpha). After 7 d, the number of cells exhibiting typical antigen-presenting cell (APC) morphology was equal in both groups, and fluorescence in situ hybridization (FISH) analysis confirmed that the APCs generated with GM/IFN-alpha were of leukaemic origin. Phenotypically, both sets of APCs expressed typical surface markers; however, CD86, CD83, CD11c, HLA-ABC and HLA-DR expression was significantly higher in the GM/IFN-alpha APCs, whereas CD1a expression was significantly lower. In mixed lymphocyte reactions (MLR), GM/IFN-alpha APCs stimulated the proliferation of allogeneic T cells significantly better than GM/IL-4 APCs. However, both groups of APCs stimulated autologous T-cell proliferation equally. Finally, we assessed the ability of GM/IFN-alpha APCs to induce a leukaemia-specific cytotoxic T-cell response. Some samples generated cytotoxic T lymphocytes (CTLs) that specifically lysed bcr-abl-positive target cells. These data show that the combination of GM-CSF and IFN-alpha, when used in vitro, induces the differentiation of malignant APCs with potent T-cell stimulatory capacity. Although there is no in vivo evidence to support these findings, it is possible that, when administered to CML patients, GM-CSF in combination with IFN-alpha results in the generation of highly stimulatory leukaemic APCs.
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PMID:Interferon alpha in combination with GM-CSF induces the differentiation of leukaemic antigen-presenting cells that have the capacity to stimulate a specific anti-leukaemic cytotoxic T-cell response from patients with chronic myeloid leukaemia. 1112 8

Several signaling cascades are engaged by expression of the p210 bcr-abl tyrosine kinase, and evidence suggests that these signals drive leukemogenesis. In this report, signaling pathways were examined and compared between cells derived from leukemic patients and cells expressing a bcr-abl construct (MBA). The effects of acute inhibition of bcr-abl with STI-571 on these signals and the survival of bcr-abl-expressing cells were also evaluated. Expression of bcr-abl in interleukin-3 (IL-3)/granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent Mo7e cells (MBA) resulted in growth factor independence, constitutive activation of Stat-5 phosphorylation, engagement of mitogen-activated protein (MAP) kinase signals, and increased expression of PTP1B and bcl-x(L). STI-571 inhibited cell growth and induced apoptosis in bcr-abl-expressing cells (MBA, K562, BV-173, KBM5) but not in bcr-abl(-) tumor cells (Mo7e, KG-1, ME-180, Daudi). STI-571-mediated apoptosis correlated with the inhibition of Stat-5 and MAP kinase activation and a reduction in overexpressed bcl-x(L) but not in PTP1B. Inhibitor had no effect on IL-3/GM-CSF-dependent Mo7e cell signaling and did not prevent activation of the other Jak/Stat pathways (interferon alpha, IL-3/GM-CSF). However, neither IL-3 nor GM-CSF could reactivate Stat-5 after the STI-571-mediated inhibition of bcr-abl. Expression of the common beta-chain of the IL-3/GM-CSF receptor was down-regulated in Stat-5-activated myeloid leukemic cells, suppressing IL-3/GM-CSF signal transduction and the ability of these cytokines to provide apoptotic protection. These studies suggest that bcr-abl activates cytokine-independent mechanisms of survival while inactivating intrinsic cytokine signaling cascades, making bcr-abl(+) myeloid cells vulnerable to apoptosis after bcr-abl inactivation.
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PMID:Down-regulation of interleukin-3/granulocyte-macrophage colony-stimulating factor receptor beta-chain in BCR-ABL(+) human leukemic cells: association with loss of cytokine-mediated Stat-5 activation and protection from apoptosis after BCR-ABL inhibition. 1131 80


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