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)

Tumor necrosis factor (TNF alpha and TNF beta) and interleukin-1 (IL-1) are mediators of immunity and inflammation that induce different, but partially overlapping responses in human endothelial cells (HEC). We compared the effect of purified recombinant human TNF alpha, TNF beta and IL-1 on the production of platelet-activating factor (PAF) in HEC. After 30-60 min of treatment with TNF alpha or TNF beta, HEC produce and partially release considerable amounts of PAF, which reach a maximum after 4-6 h. In HEC treated with IL-1 PAF production is detectable after 2 h and peaks at 8-12 h. More than twice as much PAF is produced in response to optimal concentrations of TNF alpha than in response to TNF beta or IL-1. However, PAF synthesis is stimulated by lower molar concentrations of IL-1 than TNF alpha and TNF beta. The ability to induce PAF synthesis in HEC seems to be restricted to these three cytokines, as shown by negative results obtained with other cytokines that activate HEC (interferons, granulocyte- and granulocyte-macrophage colony-stimulating factor, epithelial growth factor, fibroblast growth factor, transforming growth factor beta), or participate in the inflammatory process (IL-6, platelet-derived growth factor).
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PMID:Selected cytokines promote the synthesis of platelet-activating factor in vascular endothelial cells: comparison between tumor necrosis factor alpha and beta and interleukin-1. 213 80

We investigated the ability of the purified recombinant human cytokines: tumor necrosis factor-alpha (rTNF), granulocyte-macrophage colony-stimulating factor (rGM-CSF), interleukin-1 beta (rIL-1), interleukin-3, and tumor necrosis factor-beta (rTNF-beta) to stimulate neutrophil adherence (NA) to basement membranes (BMs) of stratified squamous epithelia pretreated with autoantibodies (ABM) specific for the BM matrix protein, type-VII collagen. rTNF, rGM-CSF, rIL-1, and rTNF-beta, but not IL-3, stimulated NA and stimulation was ABM- and cytokine-concentration-dependent. Stimulation was cytokine-specific and not due to endotoxin since it was significantly inhibited by cytokine-specific antibodies but not by polymyxin B (PB). rTNF and rGM-CSF were the most potent stimulators, were effective at concentrations less than 0.067 ng/ml, and stimulated NA greater than 600%. Relative potency was: rTNF = rGM-CSF greater than rTNF-beta greater than rIL-1. Stimulation by rTNF was due to a rapid, time-dependent effect on the neutrophil, and NA appeared to be dependent, in part, on the low-affinity neutrophil receptor for IgG, Fc(gamma)RIII, because it could be specifically inhibited by monoclonal antibody (3G8) to Fc(gamma)RIII. These results suggest that rTNF, rGM-CSF, rIL-1, and rTNF-beta may contribute individually or in combination to immune-mediated inflammation and tissue injury by stimulating immune adherence of neutrophils to tissue-bound autoantibodies and immune complexes.
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PMID:Recombinant human cytokines stimulate neutrophil adherence to IgG autoantibody-treated epithelial basement membranes. 219 82

Activated polymorphonuclear neutrophilic granulocytes (PMN) play an important role in propagation of inflammatory reactions and are capable of mediating tissue damage particularly by release of reactive oxygen species and lysosomal contents. Cytokines produced by monocytes as well as epidermal cells were recently shown to modulate PMN function. Therefore, the effect of immunomodulating cytokines on the oxidative metabolism of isolated human PMN was tested by functional as well as ultrastructural criteria. The following recombinant human cytokines were tested: tumor necrosis factor (TNF alpha), lymphotoxin (TNF beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, G-CSF, PDGF, TGF-beta, interleukin-1 (IL-1) alpha and beta, IL-2, IL-3, IL-4, IL-5, IL-6, MONAP/MOC/NAF (IL-8), interferon-alpha and -gamma. Only TNF alpha, TNF beta and GM-CSF were found to be direct stimuli of the oxidative burst in human PMN whereas IL-3, IL-5, and IL-8 were active only at extremely high concentrations. None of the other cytokines tested induced any significant effect on isolated human PMN at physiological concentrations. The results clearly demonstrate that only selected cytokines are capable of inducing a long lasting activation of PMN oxidative metabolism. Release of these mediators represents a specific signal for PMN activation in inflammatory disease states.
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PMID:Activation of the oxidative metabolism in human polymorphonuclear neutrophilic granulocytes: the role of immuno-modulating cytokines. 225 41

Limiting dilution analysis of granulocyte-macrophage progenitor cells was performed by using adherent and T cell-depleted normal human bone marrow and the recombinant human growth factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Estimated frequencies for progenitor cells responding to G-CSF were one in 489 for colonies scored at day 7, and one in 1,015 for day 14 colonies. For GM-CSF the frequencies were one in 1,407 (day 7) and one in 574 (day 14). The effects of tumor necrosis factor (TNF) and lymphotoxin (LT) on the frequency of progenitors responding to either G-CSF or GM-CSF was determined. Both TNF and LT inhibited the response of cells to G-CSF, and in these cultures the frequency of progenitor cells that responded to G-CSF was reduced to less than one in 100,000 cells. In contrast, the frequency of cells able to form colonies in cultures stimulated with GM-CSF was unaltered by either cytotoxin. This differential sensitivity to cytotoxins suggests that either G-CSF and GM-CSF are acting on separate granulocyte progenitor populations or that TNF and LT selectively influence the biochemical pathways associated with the activation of receptors for G-CSF.
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PMID:Human granulocyte-macrophage progenitors and their sensitivity to cytotoxins: analysis by limiting dilution. 244 99

CD28 is a 44-kDa glycoprotein expressed as a homodimer on the surface of a major subset of human T cells. Previous studies have demonstrated that the binding of monoclonal antibodies to the CD28 surface antigen can augment the proliferation of purified human T cells stimulated with suboptimal doses of mitogens or anti-T-cell receptor/CD3 complex antibodies. In this report, we show that CD28 stimulation augments T-cell immune responses by specifically inducing a 5- to 50-fold enhancement in the expression and secretion of interleukin 2, tumor necrosis factor type alpha, lymphotoxin, interferon gamma, and granulocyte-macrophage colony-stimulating factor in normal human T cells stimulated to proliferate by crosslinking of the T-cell receptor/CD3 complex. This CD28-mediated induction of lymphokine/cytokine gene expression occurred even in T cells stimulated with optimal concentrations of mitogens or anti-T-cell receptor/CD3 antibodies, although under these conditions CD28 activation failed to enhance the proliferative response. The activation pathway induced by stimulation of CD28 is distinct from other biochemical pathways that induce lymphokines/cytokines because CD28 stimulation can induce lymphokine/cytokine gene expression in the presence of the immunosuppressant cyclosporine. Together these data suggest that the CD28 cell surface molecule is part of a distinct activation pathway that specifically modulates the expression of multiple lymphokine/cytokine genes.
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PMID:CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. 246 50

The monocytic tumour, THP-1, expresses many of the properties of monocytes, both by cell surface staining and its capacity to produce monokines. It was used as a source of homogenous monocytic cells as a model to determine whether a variety of highly purified or recombinant cytokines could induce HLA-DR expression and the production of interleukin-1 (IL-1). Interferon-gamma (IFN-gamma) alone induced HLA-DR. Tumour necrosis factor (TNF), lymphotoxin (LT) and granulocyte-macrophage colony-stimulating factor (GM-CSF) alone were able to induce IL-1 but not HLA-DR. When IFN-gamma was combined with TNF, induction of HLA-DR and IL-1 was enhanced in a synergistic manner. These effects were detectable at a pretranslational level as synergistic effects were observed on DR alpha mRNA and IL-1 beta mRNA levels. The results demonstrate the specificity of IFN-gamma as the inductive stimulus for HLA-DR expression by THP-1 cells. As IFN-gamma and TNF are products of activated T cells, the synergistic role for these molecules in macrophage activation is discussed.
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PMID:Effect of cytokines on HLA-DR and IL-1 production by a monocytic tumour, THP-1. 249 5

Two lymphokines that contribute to induction of cell differentiation in promyelocytic HL-60 leukemia cells by human T-cell lymphoma HUT-102 cells were identified previously. The lymphokines identified in the differentiation-inducing preparation were interferon-gamma (IFN-gamma) and lymphotoxin. To determine the remaining component(s) of this differentiation-inducing activity, we used gene-cloned (recombinant) forms and antibodies of lymphokines. The differentiation-inducing activity of the HUT-102 cells was not completely neutralized by the antibodies, suggesting that an additional lymphokine(s) is involved. Granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with retinoic acid induced differentiation of the HL-60 cells in a dose-dependent manner. Furthermore, the activity of the differentiation-inducing factors was partially inhibited by anti-GM-CSF antibody and completely inhibited by the combination of antibodies to lymphotoxin, IFN-gamma, and GM-CSF. These results indicate that, in addition to IFN-gamma and lymphotoxin, GM-CSF is the third major component released by HUT-102 cells for inducing differentiation of HL-60 cells.
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PMID:Identification of components of differentiation-inducing activity of human T-cell lymphoma cells by induction of differentiation in human myeloid leukemia cells. 249 90

It is clear from extensive in vitro data that different subsets of lymphocytes stimulate and inhibit the growth of hematopoietic stem and progenitor cells. In order to clarify the complexity of the network between regulatory lymphocytes and hematopoietic target cells, we have examined the stimulatory and inhibitory effects derived from different lymphoid subsets. The regulatory influence of lymphocytes is transmitted mainly through the release of cytokines including the interleukins, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-beta and the interferons, all of which have non-specific effects on a variety of hematopoietic cells. Since these cytokines amplify the effects of other, more lineage-specific cytokines (e.g., erythropoietin, thrombopoietin and granulocyte or macrophage colony-stimulating factor) on the proliferation and differentiation of progenitor cells, the present review supports the conclusion that lymphoid subsets play a critical role in ensuring an optimal hematopoietic response to specific demands.
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PMID:Lymphoid cell regulation of hematopoiesis. 264 74

We have studied the possible role of various cytokines and growth factors on the in vitro interleukin-2 (IL-2)-dependent development of natural killer (NK) cells from bone marrow precursors. Our results indicate that tumor necrosis factor alpha and lymphotoxin augment the generation of NK cells. In contrast, interleukin-4, transforming growth factor beta and granulocyte-macrophage colony-stimulating factor significantly inhibit this phenomenon. Other factors tested, such as epidermal growth factor and fibroblast growth factor, did not detectably influence the IL-2-dependent development of NK cells.
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PMID:Effect of various cytokines and growth factors on the interleukin-2-dependent in vitro differentiation of natural killer cells from bone marrow. 265 22

Colony-stimulating factors (CSFs) are pivotal for proliferation and function of hematopoietic cells. We found that lymphotoxin, a product of activated lymphocytes, stimulates accumulation of granulocyte-macrophage (GM)-CSF and macrophage (M)-CSF proteins and mRNAs in fibroblasts. An increase in GM- and M-CSF mRNA levels occurred within 2 hours after addition of 1,000 U/mL lymphotoxin and levels plateaued over the next 24 hours. Tumor necrosis factor alpha (TNF alpha) was about five times more potent than lymphotoxin at low concentrations, and was nearly 1.5 to to 2 times more potent at maximally stimulating concentrations of the cytokines. Stimulation by lymphotoxin did not require either new protein synthesis or protein kinase-C stimulation. Stability studies of GM- and M-CSF transcripts in fibroblasts showed that M-CSF mRNA was five times more stable (half-life [t 1/2], 100 minutes) than GM-CSF mRNA (t 1/2, 20 minutes). Stability of these mRNAs was unchanged after stimulation of the cells with lymphotoxin. In addition, exposure of cells to 12-O-tetradecanoylphorbol 13-acetate did not alter stability of M-CSF mRNA but markedly prolonged the stability of GM-CSF mRNA. This is consistent with data showing that the AT-rich consensus region in the 3' untranslated region of many transiently expressed cytokines including GM-CSF but not M-CSF, play a major role in their mRNA stability. Our results suggest that activated lymphocytes can affect hematopoietic cell function and growth by stimulating production of CSFs by mesenchymal cells.
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PMID:Lymphotoxin: stimulation and regulation of colony-stimulating factors in fibroblasts. 267 16


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