Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

Recent studies have indicated that airway inflammation in atopic asthma is characterized by T-cell activation and local eosinophilia, but it is unknown whether this also applies to nonatopic asthma. In this study, the cytokine mRNA profile and activation status of inflammatory cells in bronchoalveolar lavage fluid (BALF) of eight nonallergic patients with symptomatic asthma and eight nonallergic healthy controls were compared using the message amplification phenotyping (MAPPing) with the polymerase chain reaction (PCR) procedure and immunocytochemical evaluation. Asthmatics had an increasing number of inflammatory cells in BALF, including activated eosinophils (EG2-positive) (p less than 0.001) and activated T cells (CD25-positive) (p less than 0.001). Activated T cells from five of the eight asthmatic patients and from one control subject expressed high levels of interleukin 5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF). All the asthmatic patients had increased numbers of monocytes in their BALF (p less than 0.002) and those cells invariably showed increased expression of interleukin 1 beta (IL1 beta) transcripts. In five patients they also expressed appreciable levels of IL-6 and GM-CSF mRNA. IL-5 and GM-CSF can induce local activation of eosinophils, and IL-1 beta and IL-6 are known to promote T-cell activation and proliferation. Thus, there is an increased production of cytokines with inflammatory properties in the airways of patients with nonatopic symptomatic asthma, which may contribute to the persistence of inflammation, and monocytes and activated T cells are important sources of these cytokines.
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PMID:Cytokine mRNA profile and cell activation in bronchoalveolar lavage fluid from nonatopic patients with symptomatic asthma. 151 85

Recombinant interleukin 4 (IL4) down-regulates the expression of CD14 on normal human monocytes, as assessed by flow cytometry, binding assays with radiolabeled anti-CD14 monoclonal antibody (mAb), and immunoprecipitation of 125I-labeled monocytes with anti-CD14 mAb. In parallel, CD23 expression on monocytes was strongly increased by IL4 stimulation, as assessed by both flow cytometry and immunoprecipitation. Down-regulation of surface CD14 was first detectable after 24-36 h of incubation with rIL4, and was almost complete after 4 days of culture. None of the other recombinant lymphokines tested (IL1, IL2, IL3, IL5, IL6, interferon-gamma, tumor necrosis factor alpha and beta, granulocyte-macrophage colony-stimulating factor) decreased CD14 expression. Metabolic labeling studies with [35S]methionine showed that both the membrane-associated and the soluble form of CD14 are decreased by IL4 stimulation. Northern blot analysis showed that incubation of monocytes with IL4 induced a marked decrease in CD14 mRNA. Nuclear run-off assays revealed that the IL4-dependent down-regulation of CD14 resulted from decreased transcription. Thus, IL4 exerts specific and opposite effects on the expression of monocytic antigens.
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PMID:Interleukin 4 down-regulates the expression of CD14 in normal human monocytes. 170 91

Using long-term culture techniques, it has been shown that stromal cells in the marrow microenvironment are essential for the continued production and self-renewal of hematopoietic stem cells. We previously reported the development of a methylcellulose colony assay for a population of marrow stromal progenitors called CFU-RF. In this paper, a method is described for subculturing cells from individual CFU-RF-derived colonies to allow conditioned medium production (StCM). StCM, prepared in this way, was found to possess an erythroid lineage-specific activity that stimulated the formation of macroscopic erythroid colonies in cultures containing erythropoietin (epo). Using dose-response curves, the KG1 colony assay, and antibody neutralization, it was shown that the activity could not be attributed to interleukin 3 (IL3) or granulocyte-macrophage colony-stimulating factor (GM-CSF). However, it was further shown that a monolayer of stromal cells, which had earlier been producing the erythroid activity, could be stimulated by IL1 to produce granulocytic colony-stimulating activity, but only as long as IL1 was present in the culture medium. These findings indicate a mechanism whereby the same stromal population could be modulated to promote growth and differentiation of different hematopoietic lineages.
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PMID:Erythroid lineage-specific activity in conditioned medium derived from cloned human marrow stromal cells (CFU-RF). 191 73

Human osteoblast cultures derived as out-growths from trabecular bone released tumor necrosis factor (TNF alpha) upon stimulation of the cells with human recombinant interleukin 1 (IL1; 10(-13)-10(-11) M), human recombinant granulocyte-macrophage colony-stimulating factor (100-1000 U/ml), and bacterial lipopolysaccharide (5-500 ng/ml). The osteotropic hormones 1,25-dihydroxyvitamin D3, PTH, and calcitonin had no effect on TNF production. The TNF released by the osteoblasts was identified as TNF alpha, using a specific anti-TNF alpha monoclonal antibody to neutralize its activity. Immunohistochemical staining of the cells using the same antibody revealed that all of the cells in the cultures were capable of producing TNF alpha, including those that also expressed alkaline phosphatase activity. Immunoreactive protein could be detected in the perinuclear region when cells were cultured in the presence of monensin, suggesting accumulation of newly synthesised protein in the Golgi apparatus. These results suggest that human osteoblasts, which have been shown previously to respond to TNF alpha, can synthesize and release TNF in response to IL1 and granulocyte-macrophage colony-stimulating factor. TNF may, therefore, not only have a pathological role in conditions of chronic inflammation, but also may act as a local paracrine or autocrine regulator of osteoblast function.
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PMID:Production of tumor necrosis factor by human osteoblasts is modulated by other cytokines, but not by osteotropic hormones. 240 45

We previously reported that administration of a streptococcal preparation (OK-432) inhibited insulitis and development of autoimmune diabetes in nonobese diabetic (NOD) mice and BB rats as animals models of insulin-dependent diabetes mellitus. In this study, we screened various cytokines that could be induced by OK-432 in vivo, for their preventive effect against diabetes in NOD mice. Among recombinant mouse IFN gamma, human IL1 alpha, human IL2, mouse granulocyte-macrophage colony-stimulating factor and human TNF alpha, only human TNF alpha suppressed insulitis and significantly (P less than 0.001) inhibited development of diabetes. NOD mice were the lowest producers of the mRNA of TNF and serum TNF on stimulation with OK-432 or with IFN gamma plus LPS, compared with C57BL/6, C3H/He, and Balb/c mice. The results imply a role for low productivity of TNF in the pathogenesis of autoimmune diabetes in NOD mice.
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PMID:Recombinant human tumor necrosis factor alpha suppresses autoimmune diabetes in nonobese diabetic mice. 279 65

The possibility that production of some cytokines in the carcinoma microenvironment is associated with the presence and differentiation of cells belonging to the dendritic cell (DC)/Langerhans' cell (LC) lineage was investigated. Immunohistochemical examination showed the presence of intraepithelial LCs (CD1a- and S100-positive cells) in 6 of 10 squamous cell carcinomas and in 8 of 10 adenocarcinomas. Langerhans' cells were mainly located close to lymphoid aggregates. In situ hybridization performed in four cases (three LC positive and one LC negative) of squamous cell carcinoma and in five cases (four LC positive and one LC negative) of adenocarcinoma showed that some mononuclear cells in the interstitium displayed hybridization with granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF alpha), and interleukin 1-beta (IL1 beta) cDNA probes. Only in LC-positive carcinomas did epithelial cells close to lymphoid aggregates display small amounts of GM-CSF and TNF alpha mRNA expression. Immunohistochemical analysis performed in the 20 cases of lung carcinoma showed that epithelial cells in tumors with lymphoid aggregates and LCs were immunoreactive with antihuman GM-CSF monoclonal antibody. Specimens negative for GM-CSF contained very few LCs. Northern blot analysis was used to investigate GM-CSF, TNF alpha, IL1 alpha, and IL1 beta mRNA expression in six human lung carcinoma cell lines. A constitutive expression of TNF alpha mRNA was found in all of them, whereas only three showed a low constitutive expression of GM-CSF mRNA. In the latter three cell lines treatment with phytohemagglutinin (PHA)-stimulated peripheral blood lymphocyte (PBL) supernatant (PHA-SUP) upregulated GM-CSF mRNA expression and induced that of IL1 alpha mRNA. Carcinomatous epithelial cells producing small amounts of cytokines could promote the recruitment of cells of DC/LC lineage. Subcellular factors produced by reactive lymphocytes and/or macrophages may influence the production of GM-CSF and IL1 alpha by various epithelia. Up-regulation of this production could favor the arrival and differentiation of DCs and activate LC functions.
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PMID:Role of cytokines in distribution and differentiation of dendritic cell/Langerhans' cell lineage in human primary carcinomas of the lung. 763 48

We analyzed the response of human astrocytoma cell line U373-MG to various cytokines by measuring the production of interleukin-6 (IL6) mRNA and cytokine protein. Interferon gamma (IFN gamma), transforming growth factor beta 1 (TGF-beta 1), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-colony-stimulating factor (G-CSF) did not induce IL6 mRNA production; however, IL6 mRNA expression and protein production was strongly induced by IL1 alpha and to a lesser extent by IFN alpha. The IL6 mRNA expression induced by IL1 alpha was potentiated by TGF-beta 1 and IFN alpha and slightly decreased by IFN gamma. The potentiation of cytokine mRNA accumulation by TGF-beta 1 was both time- and concentration-dependent. Induction of IL6 mRNA by IL1 alpha was optimally potentiated either if U373-MG cells were pretreated with TGF-beta 1 or if TGF-beta 1 was added within 30 min after stimulation with IL1 alpha. The potentiation of IL6 mRNA by TGF-beta 1 required de novo synthesis of an intermediate protein since treatment with cycloheximide abrogated the amount of mRNA enhanced by TGF-beta 1 without affecting IL1 alpha-driven mRNA production. Nuclear run-on analyses demonstrated increased transcriptional activity of the IL6 gene when stimulated with IL1 alpha in the presence of TGF-beta 1. However, actinomycin-D pulse chase experiments showed that TGF-beta 1 did not increase the stability of IL6 mRNA. Thus, in concert, the results demonstrate that TGF-beta 1 potentiates IL6 production in astrocytoma cells by promoting the transcriptional activity of the IL6 gene and requires coexpression of new proteins. Since cytokines can provide potent mitogenic signals to tumor cells, the results presented here further suggest that the antitumor effect of combination cytokine therapy might partly depend on heterotypic interactions between tumor cells and cytokines.
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PMID:Transforming growth factor beta-1 (TGF-beta 1) potentiates IL1 alpha-induced IL6 mRNA and cytokine protein production in a human astrocytoma cell line. 805 3

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

Interleukin 6 (IL6) secretion by blast cells derived from peripheral blood of patients with acute myelogenous leukemia (AML) was characterized. IL6 secretion showed a wide variation both when AML blasts were cultured in medium alone and in the presence of exogenous cytokines. The level of IL6 secretion was significantly correlated to secretion of other cytokines (IL1 alpha, IL1 beta, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha). IL1 beta, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor and stem cell factor increased IL6 secretion, whereas IL4 caused decreased IL6 secretion together with increased release of IL1 receptor antagonist.
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PMID:Effects of hematopoietic growth factors on interleukin 6 secretion by blast cells derived from acute myelogenous leukemia patients. 887 13

Proliferation of ramified microglia is a common phenomenon in brain pathology, but little is known about how this is regulated. In the current study, we examined the effect of different cytokines on the proliferation of ramified microglia in vitro using a combination of autoradiography for [3H]-thymidine and immunocytochemical techniques. Ramified microglia were obtained using a 10-day co-culture on top of a confluent astrocyte monolayer. Addition of macrophage colony-stimulating factor (MCSF), granulocyte-macrophage colony-stimulating factor (GMCSF), and interleukin-3 (IL3), stimulated the proliferation of ramified microglia, with a 7.2-fold, 3.5-fold, and 1.5-fold increase, respectively. Of all the other cytokines tested (IL1, IL2, IL4, IL6, IL10, interferon-gamma (IFNgamma), leukemia inhibitory factor (LIF), and tumor necrosis factor-alpha (TNFalpha) only IL1 strongly enhanced proliferation. However, this effect of IL1 was indirect and could be neutralized by antibodies against MCSF and GMCSF. IL2, IL4, IL10, TNFalpha, and IFNgamma inhibited microglial proliferation. The great number of inhibitory cytokines could point to the importance of containing microglial proliferation in the central nervous system.
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PMID:Proliferation of ramified microglia on an astrocyte monolayer: characterization of stimulatory and inhibitory cytokines. 927 47


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