Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ethanol intoxication has been associated with bacterial pneumonia and tuberculosis. More recently, ethanol was shown to impair the capacity of pulmonary macrophages to produce superoxide anion and tumor necrosis factor (TNF). Furthermore, exposure to ethanol compromises macrophage's ability to respond to stimulation with TNF and granulocyte-macrophage colony-stimulating factor (GM-CSF), and kill an intracellular pathogen, Mycobacterium avium. Based on these previous findings, we examined whether exposure to ethanol affects superoxide anion production, synthesis of cytokines, and expression of membrane receptors to TNF on human monocyte-derived macrophages. Brief exposure to 10 or 50 micrograms/dl of ethanol significantly reduced the macrophage's response to a subsequent stimulus with phorbol ester (phorbol-12-myristate-13-acetate, PMA), and this unresponsive state lasts for approximately 6 h following removal of ethanol. When macrophages were then treated with lipopolysaccharide (LPS) in the presence of ethanol, high concentrations of TNF and GM-CSF were produced, but subsequent stimulation with LPS (second stimulus) was associated with significant impairment on synthesis and release of both TNF and GM-CSF. In addition, although ethanol had no effect on TNF binding to resting macrophages and to macrophages infected with M. avium, ethanol significantly reduced the expression of TNF receptors on interferon-gamma-stimulated macrophages. The ethanol-induced inhibition of macrophage function suggests potential mechanisms for suppression of the host's immune response and consequently increased susceptibility for infectious diseases.
 ...
PMID:Ethanol affects release of TNF and GM-CSF and membrane expression of TNF receptors by human macrophages. 166 88

Chronic ethanol ingestion predisposes to tuberculosis and bacterial pneumonia. Mycobacterium avium complex (MAC) organisms cause bacteremia in patients with AIDS. Cultured human monocyte-derived macrophages and murine Kupffer cells were exposed to 10-100 micrograms/dl ethanol; significantly greater intracellular growth of MAC strains 100 (serovar 8) and 101 (serovar 1) occurred in ethanol-treated cells than in controls (range, 58% +/- 7%-70% +/- 5%; P less than .05 for 50 and 100 micrograms/dl ethanol vs. control). Both cell types, when treated with 10(3) units/ml recombinant tumor necrosis factor (TNF) or 10(2) units/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) in the presence of 10-100 micrograms/dl ethanol, killed significantly fewer MAC than controls (49% +/- 12% decrease for GM-CSF and 57% +/- 16% for TNF; P less than .05 for all comparisons). C57BL black mice infected intravenously with MAC strain 101 were given ethanol as 4% of total calories daily; after 21 days they had greater numbers of MAC in blood, liver, and spleen than controls. Ethanol's effects on the interaction between the host and MAC favor progressive infection.
 ...
PMID:Ethanol augments intracellular survival of Mycobacterium avium complex and impairs macrophage responses to cytokines. 203 94

The generation of diradylglycerol (DRG) and phosphatidic acid (PdtOH) was investigated in neutrophils primed with granulocyte-macrophage colony-stimulating factor (GM-CSF). Mass accumulation of DRG and PdtOH was measured using reversed-phase high performance liquid chromatography and thin layer chromatography, respectively. GM-CSF had no direct effect on the levels of PdtOH and DRG, but it increased PdtOH generation and the late phase of DRG accumulation in human neutrophils stimulated with FMLP. The elevation of the mass of PdtOH peaked approximately 100 s and clearly preceded that of DRG, which peaked at 150 s. The diacylglycerol kinase inhibitor R59022 enhanced the sustained increase in DRG but did not produce a parallel inhibition in PdtOH production. GM-CSF was without effect on the level of inositol 1,4,5-triphosphate [Ins(1,4,5)P3] and did not affect the liberation of Ins(1,4,5)P3 induced by FMLP. These findings exclude the involvement of the PtdIns(4,5)P2-specific phospholipase C/diacylglycerol pathway in the sustained phase of DRG accumulation. The early (30-s) appearance of PdtOH clearly suggests that GM-CSF enhanced FMLP receptor-linked phospholipase D (PLD) generation of PdtOH. PLD was assessed more directly by formation of labeled phosphatidylethanol (PEt) through PLD capacity of catalyzing a trans-phosphatidylation in presence of ethanol. The formation of PEt associated with a concomitant decrease in PdtOH directly demonstrated that the mechanism by which GM-CSF enhances PdtOH production is activation of a PLD active on phosphatidylcholine. This study provides evidence that the mechanism of action of GM-CSF involves upregulation of PLD activity leading to enhanced generation of PdtOH and DRG in FMLP-stimulated neutrophils. These findings may provide the basis for several of the priming effects of GM-CSF.
 ...
PMID:Involvement of a phospholipase D in the mechanism of action of granulocyte-macrophage colony-stimulating factor (GM-CSF): priming of human neutrophils in vitro with GM-CSF is associated with accumulation of phosphatidic acid and diradylglycerol. 220 47

Si-Jun-Zi-Tang is one of the widely used Chinese herbal medicines. In this study, human peripheral blood monocytes were treated in vitro with 50% hot ethanol extract of Si-Jun-Zi-Tang and its four major ingredients (Dangshen, Baizhu, Gancao and Fuling). The concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the culture supernatant at 3 hours and 18 hours were measured using an ELISA. Dangshen and Gancao significantly suppressed GM-CSF secretion in a dose-dependent manner. Baizhu showed no statistically significant effect on GM-CSF secretion 18 hours after in vitro drug-treatment. Fuling, by contrast, significantly augmented GM-CSF secretion in a dose-dependent manner after 18 hours of drug treatment. Si-Jun-Zi-Tang showed a suppressive effect on GM-CSF secretion at 3 hours but significantly augmented GM-CSF secretion when the cells were treated with 8 mg/ml of the drug for 18 hours. The data suggested that Si-Jun-Zi-Tang might modulate hematopoiesis and immune response via regulating GM-CSF secretion, and the presence of Fuling in Si-Jun-Zi-Tang could counteract the suppressive effect of Dangshen and Gancao on GM-CSF secretion.
 ...
PMID:Si-jun-zi-tang regulate granulocyte macrophage colony-stimulating factor secretion by human peripheral blood mononuclear cells. 873 81

Human acute myelogenous leukemia cells (HL-60 cells) can be induced to differentiate to neutrophils by exposure to dibutyryl-cyclic AMP. The differentiation of HL-60 cells allowed the mitogen-activated protein kinases p38 and p44/p42 to be rapidly and transiently activated upon stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP). Western blot analysis using phosphospecific p38 and p44/p42 mitogen-activated protein kinase antibodies showed that increasing concentrations of ethanol or 1-butanol but not 2-butanol (0.05-0.5%) inhibited fMLP-induced p38 activation but did not inhibit p44/p42 activation. These data indicated that activation of phospholipase D (PLD) was required for activation of p38 but not p44/p42. We compared the effect of fMLP with those of tumor necrosis factor alpha (TNF alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF). We found that ethanol did not inhibit p38 phosphorylation upon stimulation with either GM-CSF or TNF alpha. These results suggested that in cells stimulated with fMLP, PLD was upstream of p38. To further test the involvement of PLD, we used antisense inhibition of human PLD1 expression. Treatment with antisense oligonucleotides inhibited p38 but not p44/p42 phosphorylation. These data supported a role for human PLD1 in fMLP-induced p38 activation in neutrophil-like HL-60 cells. In addition, the results obtained with TNF alpha and GM-CSF demonstrated that p38 activation occurred independently of PLD activation.
 ...
PMID:Phospholipase D is required in the signaling pathway leading to p38 MAPK activation in neutrophil-like HL-60 cells, stimulated by N-formyl-methionyl-leucyl-phenylalanine. 1142 26

The crude polysaccharide (PFB-1) was isolated from the leaves of Perilla frutescens var. crispa by the sequential procedures with hot-water extraction, methanol reflux, and ethanol precipitation. It was further purified by anion column chromatography in order to obtain the partially purified polysaccharide (PFB-1-0). In the presence of PFB-1-0, strong cellular lysosomal enzyme activity of murine peritoneal macrophages was observed in vitro. Compared to bacterial lipopolysaccharide (LPS), its activity was relatively high. The in vitro phagocytic activity was enhanced by PFB-1-0 as the similar pattern in both gram-negative bacteria, E. coli, and gram-positive bacteria, S. aureus with a time-dependent manner. We also investigated the production of several mediators by murine peritoneal macrophages upon stimulation with PFB-1 (in vivo) or PFB-1-0 (in vitro). The levels of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha were increased in the presence of PFB-1-0 in vitro. The PFB-1 stimulated the production of interleukin (IL)-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in vivo. Results suggest that the polysaccharide from P. frutescens var. crispa represents an immunopotentiator and biological response modifiers in vitro and in vivo levels.
 ...
PMID:In vitro and in vivo effects of macrophage-stimulatory polysaccharide from leaves of Perilla frutescens var. crispa. 1191 35

The active vitamin D(3)-metabolite 1,25(OH)(2)D(3) inhibits the interleukin 4/granulocyte-macrophage colony-stimulating factor (IL-4/GM-CSF)-induced differentiation of human monocytes into dendritic cells without altering survival. Colony-stimulating factor 1 (CSF-1) is an important survival factor for cells of the monocytic lineage. We therefore investigated whether the inhibitory activity of 1,25(OH)(2)D(3) is paralleled by a regulation of CSF-1 and its receptor. Purified human monocytes were cultured together with IL-4/GM-CSF in the presence of 1,25(OH)(2)D(3), its analogue tacalcitol, the low-affinity vitamin D receptor ligand 24,25(OH)(2)D(3), or the solvent ethanol for up to 5 days. Expression of CSF-1, CSF-1R, and GM-CSF mRNA was measured by RT-PCR. Protein secretion for CSF-1 was measured by ELISA, expression of CSF-1R by flow cytometry. The results showed that 1,25(OH)(2)D(3) and tacalcitol significantly up-regulated CSF-1 mRNA-expression and protein secretion in a dose-dependent manner. The effect of 1,25(OH)(2)D(3) occurred already after 1h of pre-treatment. In contrast, CSF-1R mRNA- and cell surface-expression was down-regulated simultaneously. The solvent ethanol and 24,25(OH)(2)D(3) were without effect. GM-CSF mRNA expression was not modulated in 1,25(OH)(2)D(3)-treated cells. These data point towards a distinct and specific regulation of CSF-1 and its receptor by 1,25(OH)(2)D(3) and its analogue tacalcitol in human monocytes which parallels the inhibition of differentiation into dendritic cells without altering survival.
 ...
PMID:Vitamin D(3) and analogues modulate the expression of CSF-1 and its receptor in human dendritic cells. 1237 16

Dendritic cells (DCs), the most potent antigen-presenting cells in vivo, are now used for cancer immunotherapy during which they are usually administered to the blood of patients with cancer. However, the route of administration of DCs affects the magnitude of immune responses. This study was conducted to assess the safety of the direct administration of DCs into cancer nodules. DCs were generated by culturing peripheral blood mononuclear cells with granulocyte-macrophage colony-stimulating factor and interleukin-4 for 7 days. After confirming the phenotype and function, one hundred thousand DCs were injected directly into the cancer nodules of 4 patients with hepatocellular carcinoma (HCC) under ultrasonography guidance 48 h after the administration of 100% ethanol. All patients were monitored for any alteration in generalized condition, signs of inflammation, and liver and kidney function for the next 14 days. In addition, the final assessment of the safety of the administration of DCs into cancer nodules was performed 6 months after therapy commencement. The injection of 100% ethanol disrupted the HCC nodules in all 4 patients. DCs were distributed uniformly in the cancer nodules as assessed by ultrasonography. The administration of DCs into cancer nodules was well tolerated by all patients and there were no immediate or delayed side effects. The tumor marker decreased in one patient after the direct administration of DCs. Direct administration of DCs into the cancer nodules of patients with HCC was safe.
 ...
PMID:Administration of dendritic cells in cancer nodules in hepatocellular carcinoma. 1614 59

Continuous production of a recombinant murine granulocyte-macrophage colony-stimulating factor (MuGM-CSF) by immobilized yeast cells, Saccharomyces cerevisiae strain XV2181 (a/a, Trp1) containing plasmid palphaADH2, in a fluidized bed bioreactor was studied at a 0.03 h(-1) dilution rate and various particle loading rates ranging from 5% to 33% (v/v). Cells were immobilized on porous glass beads fluidized in an air-lift draft tube bioreactor. A selective medium containing glucose was used to start up the reactor. After reaching a stable cell concentration, the reactor feed was switched to a rich, nonselective medium containing ethanol as the carbon source for GM-CSF production. GM-CSF production increased initially and then dropped gradually to a stable level. During the same period, the fraction of plasmid-carrying cells declined continuously to a lower level, depending on the particle loading. The relatively stable GM-CSF production, despite the large decline in the fraction of plasmid-carrying cells, was attributed to cell immobilization. As the particle loading rate increased, the plasmid stability also increased. Also, as the particle loading increased from 5% to 33%, total cell density in the bioreactor increased from 16 to 36 g/L, and reactor volumetric productivity increased from 0.36 to 1.31 mg/L.h. However, the specific productivity of plasmid-carrying cells decreased from 0.55 to 0.07 mg/L.g cell. The decreased specific productivity at higher particle loading rates was attributed to reduced growth efficiency caused by nutrient limitations at higher cell densities. Both the reactor productivity and specific cell productivity increased by two- to threefold or higher when the dilution rate was increased from 0.03 to 0.07 h(-1).
 ...
PMID:Effect of particle loading on GM-CSF production by Saccharomyces cerevisiae in a three-phase fluidized bed bioreactor. 1862 33

Aloe species are traditionally prescribed for hypertension, burning, and rheumatoid arthritis. To elucidate the mechanism of the antihypertensive and anti-inflammatory activities of this herb, the ethanol fraction from A. saponaria Haw. was evaluated for antioxidative activity using xanthine-xanthine oxidase (XO) assay, 2,2-Diphenyl-lpicrylhydrazyl radical (DPPH) assay, lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cell, and antinociceptive activity using a tail-flick assay and hind paw pressure assay in cisplatin-treated hyperalgesic rats. The ethanol fraction displayed potent antioxidative activities in XO assay. In addition, ethanol fractions showed potent scavenging effects in DPPH assay. We next examined whether ethanol fractions showed anti-inflammatory activities. Ethanol fractions significantly suppressed NO production from LPS-activated RAW264.7 cells. As expected, ethanol fractions dose-dependently inhibited the messenger RNA expression of inducible NO synthase (iNOS). Moreover, ethanol fractions potently suppressed the expression of cycloxygenase (COX)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF), which are stimulated by LPS in RAW264.7 cells. In addition, ethanol fractions significantly blocked cisplatin-induced hyperalgesia using tail-flick assay and hind paw pressure test in rats. Taken altogether, ethanol extracts of aloe may be useful as a functional food or as a drug against reactive oxygen species (ROS) mediated diseases.
 ...
PMID:Evaluation of antioxidant, antinociceptive, and anti-inflammatory activities of ethanol extracts from Aloe saponaria Haw. 1868 13


1 2 Next >>