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)

Interleukin 3 (IL-3) induces proliferation and differentiation of mast cell progenitors in vitro, whereas it induces granulocytosis in vivo. In this paper, a positive feedback mechanism of granulopoiesis was studied in order to elucidate the granulocytosis induced by IL-3 in mouse. IL-3 induced expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in total bone marrow cells and a marrow adherent cell population. In fractionated marrow cell populations, a different expression pattern of induction of IL-3 stimulation was observed; GM-CSF was expressed in macrophages and fraction 1 (P < 1.061) and 2(1.061 < P 1.074) of bone marrow cells fractionated by equilibrium density centrifugation, G-CSF was expressed in macrophages and fraction 2 and 3 (1.074 < P < 1.097), and interleukin 6 (IL-6) in macrophages and fraction 1 to 3. These results indicate a hierarchical regulation of cytokine production and the existence of a positive feedback mechanism in granulopoiesis. IL-6, induced by IL-3, stimulates stem cells into cycle and induces stem cells to respond to IL-3. The stem cells differentiate to granulocyte-macrophage colony-forming cells by the combined effect of IL-3 and IL-6. IL-3 also induces GM- and G-CSF expression which in turn makes granulocyte-macrophage colony-forming cells differentiate to granulocytes. These factors organize a cytokine network in granulopoiesis.
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PMID:Induction of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) expression in bone marrow and fractionated marrow cell populations by interleukin 3 (IL-3): IL-3-mediated positive feedback mechanisms of granulopoiesis. 753 Apr 67

Peripheral blood cells from a female patient with Ph1-positive chronic myelogenous leukemia (CML) in blast crisis were serially transplanted in BALB/c nude mice for 16 passages. This in vivo cell line, designated CML-N-1, had Ph1 chromosome abnormality and BCR gene rearrangement. The cells expressed CD11b, CD13, CD33, CD34, CD38, and HLA-DR antigens until the 11th passage and subcutaneous tumors produced by these passages were composed of admixtures of immature and maturing cells that differentiated to basophils when cultured in vitro. From the 12th passage on, the tumors became composed mainly of immature cells expressing CD13, CD34, and HLA-DR, and no longer differentiated to basophils even upon in vitro culture. In contrast to the vigorous proliferation in vivo, CML-N-1 cells from any passage failed to proliferate in vitro under standard liquid culture conditions with or without growth factors, such as granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, monocyte colony-stimulating factor, interleukin 3, interleukin 6 and stem cell factor. However, a continuously growing cell line, designated CML-C-1, was established by culturing CML-N-1 cells on feeder layers of mouse bone marrow stromal cells. This mouse bone marrow stromal cell-dependent cell line showed immature cell morphology and expressed early myeloid phenotype positive for CD13, CD34, and HLA-DR. These results indicate that mouse bone marrow stromal cells provide a certain growth factor(s) active on human leukemia cells.
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PMID:Direct transplantation of chronic myelogenous leukemia cells into nude mice and establishment of a leukemic stem cell (Ph1+, CD34+) line dependent on mouse bone marrow stromal cells in vitro. 754 Jun 8

Treatment of M1 myeloid leukemic cells with interleukin 6 (IL-6) or dexamethasone (DEX), both of which induce differentiation in these cells, down-regulated expression of the apoptosis-suppressing gene bcl-2 and the apoptosis-promoting gene bax but up-regulated expression of the apoptosis-suppressing gene bcl-XL. There was a higher expression of bcl-XL in cells treated with DEX or DEX plus IL-6 compared to cells treated with IL-6 alone. The alternatively spliced bcl-X gene, bcl-Xs, which interferes with the action of bcl-2, was not expressed. Treatment with IL-6 increased the susceptibility of these cells to induction of apoptosis by Adriamycin or cycloheximide, but treatment with DEX or with IL-6 and DEX did not. Withdrawal of DEX after up-regulation of bcl-XL resulted in a decrease in bcl-XL expression and a concomitant increase in cell susceptibility to induction of apoptosis. Another myeloid leukemia that shows barely detectable expression of bcl-2 also showed up-regulated expression of bcl-XL but no change in bax after induction of differentiation with granulocyte-macrophage colony-stimulating factor, and this reduced cell susceptibility to induction of apoptosis by Adriamycin or cycloheximide. The results indicate that the related apoptosis-regulating genes bcl-2, bcl-XL, and bax are differently regulated and that up-regulation of bcl-XL expression may compensate for down-regulation of bcl-2 in the balance between genes that control apoptosis.
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PMID:Regulation of bcl-2, bcl-XL and bax in the control of apoptosis by hematopoietic cytokines and dexamethasone. 766 18

A platelet-activating factor antagonist, RP 55778, potently suppressed the induction of human immunodeficiency virus (HIV) expression in chronically infected promonocytic U1 cells. RP 55778 inhibited the production of reverse transcriptase activity in U1 cells stimulated with the transcriptionally active inducers of virus production, tumor necrosis factor alpha and phorbol 12-myristate 13-acetate. This effect was correlated only in part with a reduction in the levels of HIV RNA, suggesting that this agent was also affecting posttranscriptional levels of virus production. In this regard, RP 55778 effectively blocked the induction of HIV expression in U1 cells stimulated with interleukin 6 and granulocyte-macrophage colony-stimulating factor, which act predominantly as posttranscriptional activators of HIV expression. Finally, RP 55778 inhibited the production of endogenous tumor necrosis factor alpha in phorbol 12-myristate 13-acetate-stimulated cells, thereby interfering with an autocrine pathway of virus expression. The suppressive effects of RP 55778 on HIV expression appeared to be independent of the platelet-activating factor cell surface receptor on U1 cells. RP 55778 inhibited acute HIV replication in primary T-cell blasts and the proliferative capacity of these cells. This study suggests that RP 55778 may represent potentially useful compounds in the treatment of HIV infection.
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PMID:A platelet-activating factor antagonist, RP 55778, inhibits cytokine-dependent induction of human immunodeficiency virus expression in chronically infected promonocytic cells. 768 1

Cytokines have diverse and pleiotropic effects including immunologic, hematopoietic and pro-inflammatory activities. A total of 135 patients have been treated in a series of phase I clinical trials utilizing five different recombinant cytokines: granulocyte-macrophage colony-stimulating factor (rhuGM-CSF), interleukin 3 (rhIL-3) interleukin 4 (rhuIL-4), and interleukin 6 (rhIL-6). The toxicity, maximum tolerated dose and biologic activities were determined. Hematopoietic, immunologic and pro-inflammatory effects were noted during therapy with these agents. Prominent effects on lymphocyte and monocyte functional activities were demonstrated. The diversity of biologic effects in vivo demonstrates the pleiotropic nature of the cytokines investigated and the difficulties encountered in their in vivo evaluation.
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PMID:Pleiotropic effects of cytokines: clinical and preclinical studies. 769 57

Current evidence suggests that the gut is the chief portal of entry for organisms of the Mycobacterium avium complex (MAC) in AIDS patients. Bacterial invasion of intestinal mucosa presumably occurs through epithelial cells, and M cells in the Peyer's patches, where the bacteria have contact with immunocompetent cells such as macrophages and T and B lymphocytes. As mucosal macrophages are probably the first line of defense against MAC, we examined their ability to inhibit intracellular growth of MAC when properly stimulated. Mouse intestinal macrophages were purified, infected with MAC 101, serovar 1, and MAC 86-2686, serovar 16, and subsequently stimulated with recombinant tumor necrosis factor alpha (TNF-alpha), gamma interferon (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), or macrophage colony-stimulating factor (M-CSF). Viable intracellular bacteria were quantitated at 24 h after infection and again after 4 days of infection. Stimulation with TNF-alpha, IFN-gamma, and GM-CSF, but not M-CSF, was associated with mycobacteriostatic and/or mycobactericidal activity in macrophages. Treatment with 10(3) U of TNF-alpha, GM-CSF, and IFN-gamma per ml at 24 h prior to infection with MAC resulted in a significant enhancement in killing of MAC at 4 days after infection, compared with that observed for macrophages exposed to cytokines after infection. When stimulated with lipopolysaccharide or live MAC, intestinal macrophages had produced significantly less TNF-alpha and transforming growth factor beta than had splenic and peritoneal macrophages, although the levels of production of interleukin 6 and interleukin 10 among the three populations of cells were similar. Intestinal macrophages can be stimulated with cytokines to inhibit the intracellular growth of MAC, but they have differentiated abilities to produce cytokines which can modulate the anti-MAC immune response.
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PMID:Response to stimulation with recombinant cytokines and synthesis of cytokines by murine intestinal macrophages infected with the Mycobacterium avium complex. 782 18

We examined the effects of recombinant human erythropoietin (rhEPO), recombinant murine interleukin 3 (rmIL-3), recombinant human interleukin 6 (rhIL-6), recombinant human interleukin 11 (rhIL-11), recombinant murine leukemia inhibitory factor (rmLIF) and recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) on the growth of murine megakaryocytic cell lines. In serum-free methylcellulose culture supplemented with bovine serum albumin (BSA), the addition of rhEPO (0.1-10 U/ml), rmIL-3 (10-500 U/ml), rhIL-6 (100-10,000 U/ml), rmLIF (100-10,000 U/ml), or rmGM-CSF (10-1000 U/ml) enhanced colony growth in L8057Y5 cells, which had been maintained in protein-free culture, mostly in a dose-dependent fashion; rhIL-11 did not have any stimulatory effect at the tested doses (10-1000 U/ml). In addition, colony growth of L8057 cells, which had been maintained in serum-containing culture, was enhanced, but to a lesser extent, by the addition of these cytokines except rhEPO (the cultures were supplemented with 1% fetal bovine serum. Among the cytokines that showed growth-enhancing effects on L8057 cells, the expression of mRNAs encoding receptors for EPO, IL-6 and IL-3 was examined by northern blot analysis or reverse transcription polymerase chain reaction (RT-PCR). In both cell lines, mRNAs for EPO-R, IL-6R, gp130, IL-3R alpha and beta chains were constitutively expressed. The results suggest that L8057 and L8057Y5 cell lines have characteristics of megakaryoblastic cells in their biological responses to cytokines, as well as in the expression of cytokine receptor mRNAs, and that the growth-enhancing effects of these cytokines on the cell lines may be achieved through specific receptors. Our findings show the value of these cell lines for investigating the mechanisms of growth signal transduction in megakaryopoiesis.
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PMID:Effects of erythropoietin, IL-3, IL-6 and LIF on a murine megakaryoblastic cell line: growth enhancement and expression of receptor mRNAs. 786 46

In monocytes, the nuclear factor NF-kappa B has been invoked as an important transcription factor in the expression of cytokine genes, of cell-surface receptors and in the expression of human immunodeficiency virus. In such cells, DNA binding activity of NF-kappa B can be detected without intentional stimulation. In our studies, cells of the human monocytic line Mono Mac 6, cultured in medium containing fetal-calf serum and low levels of lipopolysaccharide (LPS), also exhibit such 'constitutive' NF-kappa B, as demonstrated by mobility-shift analysis of nuclear extracts. This nuclear NF-kappa B was still present when contaminant LPS was removed by ultrafiltration and when serum was omitted. Protein-DNA complexes of constitutive NF-kappa B are similar in mobility to the LPS-induced NF-kappa B and both are recognized by an antibody specific to the p50 subunit of NF-kappa B. By contrast, treatment of cells with pyrrolidine dithiocarbamate (PDTC) will only block LPS-induced NF-kappa B, but not the constitutive binding protein. Using LPS-free and serum-free conditions, constitutive NF-kappa B can be detected in different cell lines of the monocytic lineage (HL60, U937, THP-1, Mono Mac 1 and Mono Mac 6), but not in Molt 4 T cells or K562 stem cells. When ordered according to stage of maturation, the amount of constitutive NF-kappa B was not increased in more mature cell lines. Furthermore, when inducing differentiation in Mono Mac 6 cells, with vitamin D3, no change in constitutive or inducible NF-kappa B can be detected. Analysis of primary cells revealed substantial constitutive NF-kappa B-binding activity in blood monocytes, pleural macrophages and alveolar macrophages. The constitutive NF-kappa B appears to be functionally active, since a low level of tumour necrosis factor (TNF) transcript is detectable in monocytes, and this level can be increased by blocking transcript degradation using cycloheximide. The level of constitutive NF-kappa B in these cells is variable and is frequently found to be lower in the more mature macrophages. Constitutive NF-kappa B was not maintained by autocrine action of cytokines TNF, interleukin 6, interleukin 10, granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor, since neutralizing antibodies did not reduce constitutive DNA-binding activity. Furthermore, blockade of prostaglandin or leukotriene biosynthesis did not affect constitutive NF-kappa B.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Constitutive nuclear NF-kappa B in cells of the monocyte lineage. 799 62

Human Dexter-type culture of bone marrow (BM) cells maintains long-term hematopoiesis in the presence of an adherent stromal layer. These BM adherent cells produce hematopoietic growth factors constitutively or inducively and support developing hematopoietic cells. To elucidate the ability of cytokine production by BM adherent cells, the cytokine levels of the culture supernatant of BM adherent cells were measured by enzyme-linked immunosorbent assays. Constitutive production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL-6) by the unstimulated BM adherent cells was demonstrated. Levels of granulocyte colony-stimulating factor (G-CSF) were below detectable levels (< 10 pg/ml). The IL-6 level was significantly increased in the co-culture supernatant with KG1 cells or U937 cells (P < 0.01: P < 0.05, respectively). Even when the adherent cells and cell line cells were separated by a membrane filter, the IL-6 level was significantly higher than the control culture (P < 0.01). Co-culture with these cell lines was supposed to induce the increased production of IL-6, which was mediated by some soluble cytokines. The GM-CSF level was not increased in the supernatant co-cultured with any of the cell lines, except with K562 cells. However, K562 cells alone secreted a detectable level of GM-CSF and the increased level of GM-CSF was considered to be due to the production of GM-CSF by K562 cells. G-CSF was not detectable in the supernatant co-cultured with any cell line cells. This result indicates that the cytokine production was regulated by the interaction of BM adherent cells and some leukemic cells.
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PMID:Augmented production of interleukin 6 by co-culture of human bone marrow adherent cells and human leukemic cells. 806 59

The effects of leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) on blast progenitors from acute myeloblastic leukemia (AML) were examined using a blast colony assay in a serum-free culture system. LIF and IL-6 stimulated colony growth in 2 and 5, respectively, of 11 cases studied. The simultaneous addition of LIF with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3) or IL-6 produced a statistically significant increase of colony numbers in 3, 6 and 7 of 11 cases, respectively. Numbers of colonies increased significantly when IL-6 was added simultaneously with GM-CSF or IL-3 in 5 and 4 of 11 cases, respectively. LIF or IL-6 used in the primary culture did not significantly change the numbers of secondary colonies compared to GM-CSF. Previous exposure to LIF and IL-6 did not alter cellular phenotype or morphology, indicating that LIF and IL-6 did not induce the differentiation of fresh AML blasts.
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PMID:The effects of leukemia inhibitory factor and interleukin 6 on the growth of acute myeloid leukemia cells. 809 66

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