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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)

Endotoxin and gram-negative bacteria induce vigorous inflammatory reactions. Our previous work showed that rabbit macrophages (M phi) incubated with endotoxin produce a 45,000 dalton protein that recruited polymorphonuclear leukocytes (PMNL) into the skin of rabbits. This factor was separated from interleukin-1 (IL-1) but could not be unequivocally distinguished from rabbit tumour necrosis factor (TNF alpha). Here we have examined the human M phi cell line, THP-1, for the production of an analogous protein. After exposure to phorbol diester the THP-1 cells assumed the characteristic M phi phenotype and function. During 6 hours of culture with LPS these M phi released a factor(s) that caused PMNL recruitment into the skin of rabbits when injected intradermally, measured using 51Cr-labelled blood leukocytes. This activity, referred to as PMNL recruiting activity (PRA), was heat labile, and its production was blocked by cycloheximide, suggesting that this is most likely a de novo synthesized protein. Sephadex-G 100 and Superose-12 FPLC chromatography indicated a molecular weight in the 45,000-65,000 dalton range. The active fractions were free of IL-1 activity (less than 0.2 U/ml), and Superose-12 chromatography separated the peak of PRA, which eluted around 45,000 daltons, from TNF alpha eluting at 20,000 daltons. The peak PRA was not neutralized by antiserum to IL-1 alpha, IL-1 beta TNF alpha, IL-6, and granulocyte-macrophage colony-stimulating factor (GMCSF), indicating that it was distinct immunologically from these cytokines. The major PRA did not induce migration of rabbit or human PMNLs in vitro in a Boyden chamber chemotaxis assay, although peaks of chemotactic activity and weak PMNL recruitment in vivo were detected in fractions eluting around 15,000 daltons and 800 daltons. The generation of PRA by a human M phi cell line is analogous to that reported previously with rabbit M phi. Here we extend these observations to a human M phi system and confirm that this molecule is distinct from several other M phi cytokines and M phi chemotactic factors with inflammatory properties.
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PMID:An endotoxin-induced factor distinct from interleukin-1 and tumour necrosis factor alpha produced by the THP-1 human macrophage line stimulates polymorphonuclear leukocyte infiltration in vivo. 240 84

We tested the effect of interleukin 1 (IL-1) on the growth of leukemic blast progenitors from patients with acute myeloblastic leukemia (AML). A purified blast cell fraction depleted of both T cells and phagocytic cells was tested at different cell densities. Addition of 1 ng/ml of IL-1 alpha alone enhanced blast colony formation in 10 of 13 cases tested, and the enhancement was prominent when plated cell densities were lowered. The conditioned media (CM) from AML patients contained varied levels of IL-1 activity, and following depletion of phagocytic cells, the levels decreased markedly in all cases tested. Addition of either antiserum against IL-1 alpha or IL-1 beta reduced the IL-1 activity in CM, suggesting that AML blasts produce both IL-1 alpha and IL-1 beta. Addition of IL-1 alpha or IL-1 beta antiserum inhibited blast colony formation in a dose-dependent manner, and a combination of both antisera showed the most marked inhibition. However, the augmentation of blast colony formation was almost completely inhibited by addition of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) serum in all three cases tested. IL-1 is also devoid of this activity when tested in the presence of a combination of granulocyte CSF (G-CSF), GM-CSF, and interleukin 3 (IL-3) at an optimal concentration. These results suggest that blast cells could produce and secrete CSF(s) and/or IL-1, and that the growth-enhancing effect of IL-1 on AML blasts is indirect, via production of CSFs by leukemic cells.
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PMID:Mechanism of action of interleukin 1 on the progenitors of blast cells in acute myeloblastic leukemia. 240 55

The expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) genes by stromal cells of the hematopoietic microenvironment is regulated, in vitro, by interleukin 1 alpha (IL-1 alpha) and IL-1 beta. We reasoned that malfunction of this inductive mechanism in vivo might contribute to the intolerance of the aged to myelosuppressive therapy. We found that bone marrow fibroblasts from healthy elderly (ages 65-75 years) volunteers were less sensitive to the inductive effects of recombinant IL-1 beta than were marrow fibroblasts from younger volunteers, and we proposed that an age-related decline in sensitivity of marrow stroma to IL-1 may impair the ability of the elderly to increase production of hematopoietic growth factors under conditions of physiologic stress.
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PMID:The hematopoietic microenvironment in the elderly: defects in IL-1-induced CSF expression in vitro. 247 27

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

HTLV-I infection of peripheral mature T cells appears to induce the expression of cellular genes including those of some cytokines and their receptors. We examined the expression of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) at the mRNA level in fresh leukemic cells from 20 adult T cell leukemia patients to see whether there is any association between cytokine expression and HTLV-I expression and between their expression and clinical manifestations such as hypercalcemia or neutrophilia. IL-1 alpha, IL-1 beta and IL-3 expression was observed in 3, 7 and 1 of 20 cases examined, respectively. However, there seemed to be no association between IL-1 expression and clinical manifestations. IL-2, IL-4 and GM-CSF mRNA expression was not detected. HTLV-I viral RNA expression was detected only in one case in which IL-3 mRNA was expressed in both peripheral blood and lymph node cells and a relatively high proportion of leukemic cells expressed IL-2 receptor (p55, Tac). Thus, in the present study we could not find any correlation between cytokine expression and HTLV-I expression in peripheral blood fresh leukemic cells except in one unusual case.
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PMID:Expression of cytokine mRNA in leukemic cells from adult T cell leukemia patients. 250 74

Neutrophil accumulation and activation are early events in the inflammatory response in vivo. Using human recombinant forms of the putative inflammatory mediators interleukin-1 (IL-1) and tumour necrosis factor (TNF alpha) we were unable to detect direct effects on human neutrophil locomotion or intracellular free calcium concentration ([Ca2+]i) in vitro. Human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was able to stimulate significant locomotion, but was unable to elevate neutrophil [Ca2+]i. In contrast, supernatant from cultured human synovial cells that had been treated with human recombinant IL-1 alpha (28 pM) released a factor that stimulated both neutrophil locomotion and elevated neutrophil [Ca2+]i. Our studies demonstrate that the production of this factor is time-dependent, requiring exposure of the synovial cells to IL-1 for more than 4 hr, is not influenced by cyclo-oxygenase or lipo-oxygenase inhibition, but can be abolished by dexamethasone (100 nM) or actinomycin D (0.8 microM). The factor has a molecular weight above 10,000 and does not cross-react with anti-C5a antisera. IL-1 beta and TNF alpha were also able to stimulate its production. Our findings suggest that the neutrophil accumulation that is known to occur in response to IL-1 in vivo may be a consequence of the local production of such a factor.
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PMID:Neutrophil stimulation by recombinant cytokines and a factor produced by IL-1-treated human synovial cell cultures. 306 19

Recent studies have examined the synergistic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and hematopoietin-1 (now identified as Interleukin-1, IL-1) on bone marrow colony formation. In the present report, human peripheral blood mononuclear cells (MNCs) were stimulated in vitro with recombinant human GM-CSF (rGM-CSF) and production of IL-1 alpha, IL-1 beta, and tumor necrosis factor (TNF) was measured by specific radioimmunoassays. In the MNCs of 20 individuals, rGM-CSF's ability to induce the three cytokines was variable. Nearly all donors responded to low-dose rGM-CSF (0.02 to 2 ng/mL) with production of TNF, whereas some individuals did not produce IL-1 alpha or IL-1 beta. The MNCs from some subjects stimulated with high-dose rGM-CSF (10 to 80 ng/mL) produced as much cytokine as in response to 10 ng/mL endotoxin. Localization (ie, extracellular or cell-associated cytokine) was specific for the cytokine rather than the stimulus. Indomethacin increased the amount of cytokine produced in response to rGM-CSF for IL-1 beta and TNF but not for IL-1 alpha. In addition, interferon-gamma (INF-gamma) upregulated the amount of TNF induced by rGM-CSF in all donors examined, with variable effect on IL-1 alpha and IL-1 beta. Suboptimal levels of endotoxin incubated with rGM-CSF did not alter the amount of IL-1 produced as compared with cells stimulated with rGM-CSF alone, whereas TNF production showed either no change or a slight decrease in production. These data suggest that GM-CSF may play an important role in the host defense response by stimulating production of these cytokines.
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PMID:Production of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor by human mononuclear cells stimulated with granulocyte-macrophage colony-stimulating factor. 197 Apr 88

The purpose of this study was to determine whether human polymorphonuclear neutrophils (PMN), which share a common cell lineage with macrophages, could produce factors such as IL-1. We show by Northern blot analysis and bioassays that PMN can be induced to accumulate mRNA specific for IL-1 alpha and IL-1 beta indistinguishable in size from IL-1 mRNA synthesized by activated human macrophages and consequently to release IL-1-like activity in their culture supernatants, that could be neutralized by a mAb to IL-1. The granulocyte-macrophage colony-stimulating factor was identified as a major physiologic inducer for PMN-IL-1.
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PMID:Granulocyte/macrophage colony-stimulating factor induces interleukin 1 production by human polymorphonuclear neutrophils. 327 81

The effect of interleukin 10 (IL-10) on proliferation and cytokine secretion by acute myelogenous leukemia (AML) blast cells was investigated in vitro. IL-10 inhibited spontaneous AML blast proliferation for a majority of patients, whereas in the presence of exogenous growth factors (granulocyte-stimulating factor, G-CSF; granulocyte-macrophage colony-stimulating factor, GM-CSF; interleukin 3) the IL-10 effect on blast proliferation showed a wide variation depending on the individual AML patient. IL-10 seemed to cause an irreversible inhibitory effect on AML blasts, as inhibition could also be demonstrated when IL-10 was present only during the initial preincubation of the leukemia cells. IL-10 also inhibited AML blast colony formation. However, independent of the effect on AML blast proliferation, IL-10 decrease cytokine secretion from AML blast cells for all patients, as demonstrated for IL-1 alpha, IL-1 beta, tumor necrosis factor-alpha, GM-CSF and interleukin 6. IL-10 did not inhibit development of apoptosis in AML blasts cultured in vitro. Expression of complement receptors and capability to adhere and internalize bacteria by AML blasts were not altered by IL-10.
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PMID:Effects of interleukin 10 on blast cells derived from patients with acute myelogenous leukemia. 747 83

Interleukin (IL)-3 stimulates hemopoiesis in vitro. However, IL-3 is not normally found in bone marrow, raising doubts as to the in vivo role of IL-3. We have found that human umbilical vein endothelial cells (HUVEC) express functional high-affinity receptors for IL-3 after stimulation with tumor necrosis factor alpha (TNF-alpha), IL-1 beta, or lipopolysaccharide, and that this receptor is involved in inflammatory phenomena. TNF-alpha caused time- and dose-dependent up-regulation of mRNA for the IL-3 receptor alpha and beta chains, with maximal effects occurring 16-36 h after stimulation with TNF-alpha at 100 units/ml. Induction of mRNA correlated with protein expression on the cell surface as judged by monoclonal antibody staining and by the ability of HUVEC to specifically bind 125I-labeled IL-3. Scatchard analysis under optimal conditions of TNF-alpha stimulation revealed approximately 1500 IL-3 receptors per cell, which were of a high-affinity class (Kd = 500 pM) only. In contrast to a previous report, receptors for granulocyte-macrophage colony-stimulating factor could not be detected. IL-3 binding to TNF-alpha-activated HUVEC enhanced IL-8 production, E-selection expression, and neutrophil transmigration. The selective induction of a functional IL-3 receptor on endothelial cells suggests that, beyond hemopoiesis, IL-3 may have an important role in chronic inflammation and in allergic diseases.
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PMID:The receptor for interleukin 3 is selectively induced in human endothelial cells by tumor necrosis factor alpha and potentiates interleukin 8 secretion and neutrophil transmigration. 824 92


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