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)

Ischaemia in wounds may modulate the expression of tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The release of these and other cytokines by stimulated macrophages influences wound healing. Our aim was to examine the separate and combined effects of hypoxia and glucose deprivation on TNF-alpha and GM-CSF mRNA levels in human monocytes isolated from peripheral blood by density gradient centrifugation and purified by adherence. Cells were incubated for a 16-hour period in a hypoxic (3% O2) or normoxic (21% O2) environment in the presence or absence of glucose followed by a further 4 h under normoxic conditions in the presence or absence of lipopolysaccharide (LPS, 100 pg/ml). These different incubation conditions had no effect on cell viability, cell number, lactate dehydrogenase release or superoxide anion generation (n = 5, p > 0.05, paired t test). However, Northern hybridisation showed that hypoxia decreased the expression of GM-CSF mRNA in LPS-stimulated human monocytes by 46% (n = 9, p < 0.05, paired t test) and increased the expression of TNF-alpha by 102% (n = 7, p < 0.05, paired t test). The increase in the level of immunoreactive TNF-alpha in the cell supernatants paralleled the increase in TNF-alpha mRNA. The combination of glucose deprivation and hypoxia decreased the expression of both GM-CSF and TNF-alpha mRNA in LPS-stimulated human monocytes. Similarly, a decrease in the level of TNF-alpha in the cell supernatants was observed (n = 3-5, p < 0.05, two-way ANOVA). These data suggest that incubation conditions simulating ischaemia reduce LPS-induced cytokine expression.
 ...
PMID:Influence of hypoxia and glucose deprivation on tumour necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor expression in human cultured monocytes. 954 21

Mice with a null mutation of the betac chain of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 receptors (betac-null mice) develop an alveolar proteinosis-like lung disease. The pathogenesis of this disease is uncertain and, although a defect in alveolar macrophage function has been postulated, no previous analysis of mature hematopoietic cells in mice with alveolar proteinosis has been reported. Therefore, we undertook a functional analysis of the mature hematopoietic cell compartment in betac-null mice. In addition, we reexamined the roles of the GM-CSF receptor chain and the betac chain in signaling by GM-CSF. Neutrophils and macrophages from betac-null mice were capable of normal survival and phagocytosis in the absence of stimulus and of similar levels of nitric oxide production in response to interferon-gamma and lipopolysaccharide. GM-CSF-mediated augmentation of survival, phagocytosis, and hydrogen-ion production were absent in neutrophils from betac-null mice. Interestingly, we were unable to show any ability of the GM-CSF receptor -chain alone to mediate glucose transport in these cells. In keeping with the betac-null mice lung pathology, examination of lavage fluid from the lungs of betac-null mice showed increased cellularity. This was caused by an increase in the number of lymphocytes, neutrophils, and macrophages. Large foamy cells in the lavage fluid from betac-null mice were identified as macrophages using immunohistochemistry. Functional analysis showed that these betac-null alveolar macrophages were capable of phagocytosis but uptake of colloidal carbon and cellular adhesion were reduced. In summary, mature hematopoietic cells with a null mutation of the betac receptor were unable to perform GM-CSF-mediated hematopoietic cell functions including glucose transport, but responded normally to a range of other ligands.
 ...
PMID:Functional analysis of mature hematopoietic cells from mice lacking the betac chain of the granulocyte-macrophage colony-stimulating factor receptor. 983 17

The hematopoietic cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), Interleukin (IL)-5 and IL-3 utilise a common receptor signalling molecule, the beta common chain (beta c). This shared receptor component explains, in part the overlapping actions of these cytokines. Mice lacking beta c have a low circulating eosinophil level, have impaired eosinophilic responses to parasitic infection and develop lung disease analogous to human pulmonary alveolar proteinosis (PAP). Surprisingly however, mature hematopoietic cell function is relatively intact, although all GM-CSF-mediated mature cell responses, including glucose transport are absent. Intriguing observations suggesting altered susceptibility to some infectious agents and amelioration of responses to inflammatory stimuli, require further clarification.
 ...
PMID:The beta common chain (beta c) of the granulocyte macrophage-colony stimulating factor, interleukin-3 and interleukin-5 receptors. 1058 35

Oral recurrent aphthous ulceration (RAU) is a well-recognized complication in patients infected with human immunodeficiency virus. RAU can be progressive and destructive, causing dysphagia and secondary malnutrition. The aetiology of RAU remains unknown, and its response to available treatments is often unsatisfactory. We describe three patients with advanced AIDS who suffered from extensive RAU which failed to respond to several treatments, including topical viscous lidocaine and topical and systemic glucocorticoids. Owing to difficulties in using thalidomide (two patients had neurological conditions which precluded thalidomide use), all three patients were treated with an oral solution containing recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, 400 microg in 5% glucose 200 mL). From the first application, all three patients showed significant improvement of their lesions and amelioration of pain, and they were completely cured in a few days. No adverse effects were recorded. The patients did not show relapses of RAU over a prolonged follow-up. Controlled trials are warranted in order to establish the role of GM-CSF as a valid, alternative option for aphthous ulcerations of the mouth in AIDS patients in whom corticosteroids or thalidomide are not suitable.
 ...
PMID:Successful treatment of aphthous ulcerations in AIDS patients using topical granulocyte-macrophage colony-stimulating factor. 1065 17

Granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion from epithelial cells lining the female reproductive tract is induced during early pregnancy by ovarian steroid hormones and constituents of seminal plasma. In this study we have investigated the influence of GM-CSF on development of preimplantation mouse embryos. Blastocyst-stage embryos were found to specifically bind (125)I-GM-CSF and analysis of GM-CSF mRNA receptor expression by reverse transcriptase-polymerase chain reaction indicated expression of the low-affinity alpha subunit of the GM-CSF receptor, but not the affinity-converting beta subunit (beta(c)), or GM-CSF ligand. GM-CSF receptor mRNA was present in the fertilized oocyte and all subsequent stages of development, and in blastocysts it was expressed in both inner cell mass and trophectoderm cells. In vitro culture of eight-cell embryos in recombinant GM-CSF accelerated development of blastocysts to hatching and implantation stages, with a maximum response at a concentration of 2 ng/ml (77 pM). Blastocysts recovered from GM-CSF-null mutant (GM-/-) mice on Day 4 of natural pregnancy or after superovulation showed retarded development, with the total cell number reduced by 14% and 18%, respectively, compared with GM+/+ embryos. Blastocysts generated in vitro from two-cell GM-/- and GM+/+ embryos were larger when recombinant GM-CSF was added to the culture medium (20% and 24% increases in total cell numbers in GM+/+ and GM-/- blastocysts, respectively). Incubation of blastocysts with recombinant GM-CSF elicited a 50% increase in the uptake of the nonmetabolizable glucose analogue, 3-O-methyl glucose. In conclusion, these data indicate that GM-CSF signaling through the low-affinity GM-CSF receptor in blastocysts is associated with increased glucose uptake and enhanced proliferation and/or viability of blastomeres. Together, the findings implicate a physiological role for maternal tract-derived GM-CSF in targeting the preimplantation embryo, and suggest that defective blastocyst development contributes to compromised pregnancy outcome in GM-CSF-null mutant mice.
 ...
PMID:Granulocyte-macrophage colony-stimulating factor promotes glucose transport and blastomere viability in murine preimplantation embryos. 1125 69

Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates cellular glucose uptake by decreasing the apparent K(m) for substrate transport through facilitative glucose transporters on the plasma membrane. Little is known about this signal transduction pathway and the role of the alpha subunit of the GM-CSF receptor (alpha GMR) in modulating transporter activity. We examined the function of phosphatidylinositol 3-kinase (PI 3-kinase) in GM-CSF-stimulated glucose uptake and found that PI 3-kinase inhibitors, wortmannin and LY294002, completely blocked the GM-CSF-dependent increase of glucose uptake in Xenopus oocytes expressing the low affinity alpha GMR and in human cells expressing the high affinity alpha beta GMR complex. We identified a Src homology 3 domain-binding motif in alpha GMR at residues 358-361 as a potential interaction site for the PI 3-kinase regulatory subunit, p85. Physical evidence for p85 binding to alpha GMR was obtained by co-immunoprecipitation with antibodies to alpha GMR and p85, and an alpha GMR mutant with alteration of the Src homology 3 binding domain lost the ability to bind p85. Experiments with a construct eliminating most of the intracellular portion of alpha GMR showed a 50% reduction in GM-CSF-stimulated glucose uptake with residual activity blocked by wortmannin. Searching for a proximally generated diffusible factor capable of activating PI 3-kinase, we identified hydrogen peroxide (H(2)O(2)), generated by ligand or antibody binding to alpha GMR, as the initiating factor. Catalase treatment abrogated GM-CSF- or anti-alpha GMR antibody-stimulated glucose uptake in alpha GMR-expressing oocytes, and H(2)O(2) activated PI 3-kinase and led to some stimulation of glucose uptake in uninjected oocytes. Human myeloid cell lines and primary explant human lymphocytes expressing high affinity GM-CSF receptors responded to alpha GMR antibody with increased glucose uptake. These results identify the early events in the stimulation of glucose uptake by GM-CSF as involving local H(2)O(2) generation and requiring PI 3-kinase activation. Our findings also provide a mechanistic explanation for signaling through the isolated alpha subunit of the GM-CSF receptor.
 ...
PMID:Granulocyte-macrophage colony-stimulating factor signals for increased glucose transport via phosphatidylinositol 3-kinase- and hydrogen peroxide-dependent mechanisms. 1253 75

The aim of this study was to determine the effects of mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) on development of porcine parthenotes and nuclear transferred embryos, and on their expression of implantation-related genes. In the presence of bovine serum albumin, mGM-CSF did not increase the percentage of oocytes that developed to the blastocyst stage and at day 7 did not increase cell numbers of embryos. Addition of 2 ng/ml GM-CSF to protein-free culture medium significantly increased the compaction and blastocoel formation of 1- to 2-cell parthenotes developing in vitro. However, total cell numbers were not increased when they were cultured in the presence of GM-CSF. Semi-quantitative reverse transcriptase polymerase chain reaction revealed that mGM-CSF enhances mRNA expression of the leukemia inhibitory factor receptor, but does not influence interleukin-6 or sodium/glucose co-transporter protein gene expression in blastocyst stage parthenotes. These results suggest that mGM-CSF may enhance viability of porcine embryos developing in vitro in a defined culture medium.
 ...
PMID:Mouse granulocyte-macrophage colony-stimulating factor enhances viability of porcine embryos in defined culture conditions. 1530 96

Uterine leiomyomas, benign tumours of the human uterus, are the most common uterine neoplasm and are composed of smooth muscle with varying amounts of fibrous connective tissue. As a functional imaging modality, 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography can be used to obtain information about glucose metabolism in tissues. In this study, the findings of the F-FDG scans of four patients who were suspected of having malignant gynaecological tumours because of clinical and radiological findings and finally diagnosed as uterine leiomyoma based on histopathological examination were evaluated. Moderately intense F-FDG accumulation was detected in uterine mass localization in lower pelvis. The reason for the accumulation of F-FDG in uterine leiomyomas is not known. It may be explained by the existence of higher levels of growth factors, including basic fibroblast growth factor, transforming growth factor beta, granulocyte-macrophage colony-stimulating factor and receptors, and proliferation of smooth muscle cells in leiomatous uterus.
 ...
PMID:Uptake of 2-[18F]fluoro-2-deoxy-D-glucose in uterine leiomyoma: imaging of four patients by coincidence positron emission tomography. 1531

Glucose transport activity and its possible regulation by reactive oxygen species in two Glut1-expressing megakaryocytic cell lines, MO7e and B1647, differing in cytokine sensitivity were compared. Results show that: (1) In MO7e cells, glucose transport rate increased in response to thrombopoietin, granulocyte-macrophage colony-stimulating factor, or stem cell factor, due to a decreased Km. (2) A higher Vmax value was determined in B1647 cells, owing to the relative higher abundance of Glut1 on the plasmalemma; in these cells no change in glucose transport rate was observed on cytokine treatment. (3) The basal level of intracellular ROS was higher in B1647 than in M07e cells, where ROS production was enhanced upon cytokine exposure. (4) Basal or stimulated ROS production and Glut1 activity were significantly reduced by pretreating both cell lines with EUK-134, a superoxide dismutase and catalase mimetic. (5) In MO7e cells, EUK-134 brought back to control levels the Km values obtained on cytokine treatment, whereas in B1647 cells the antioxidant drastically reduced Vmax by decreasing the Glut1 content of the plasma membrane. Our data suggest that differences in acute regulation of glucose transport activity in the two cell lines may be related to differences in amplitude and spatial organization of ROS production.
 ...
PMID:Contribution of reactive oxygen species to the regulation of Glut1 in two hemopoietic cell lines differing in cytokine sensitivity. 1545 79

The pathogenesis of type 1 diabetes (T1D) involves the immune-mediated destruction of insulin-producing beta cells in the pancreatic islets of Langerhans. Genetic analysis of families with a high incidence of T1D and nonobese diabetic (NOD) mice, a prototypical model of the disorder, uncovered multiple susceptibility loci, although most of the underlying immune defects remain to be delineated. Here we report that aged mice doubly deficient in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) manifest insulitis, destruction of insulin-producing beta cells, and compromised glucose homeostasis. Macrophages from mutant mice produce increased levels of p40 after LPS stimulation, whereas concurrent ablation of interferon-gamma (IFN-gamma) ameliorates the disease. The administration of antibodies that block cytotoxic T lymphocyte associated antigen-4 (CTLA-4) to young mutant mice precipitates the onset of insulitis and hyperglycemia. These results, together with previous reports of impaired hematopoietic responses to GM-CSF and IL-3 in patients with T1D and in NOD mice, indicate that functional deficiencies of these cytokines contribute to diabetes.
 ...
PMID:Functional deficiencies of granulocyte-macrophage colony stimulating factor and interleukin-3 contribute to insulitis and destruction of beta cells. 1748 99


<< Previous 1 2 3 4 Next >>