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)

Diploid fibroblast (dFb) cultures were established from a total of 106 skin and serosa biopsies of human adults. Using an optimized enzymatic dissociation procedure, 10(11) dFb/cm2 skin were obtained from patients younger than 60 years after an average time of 89 +/- 8 days, with a mean population doubling time of 3.87 +/- 1.4 days. Enzymatic dissociation of skin biopsies yielded cultures of significantly higher growth capacity of dFb than those prepared by mechanical dissociation followed by spontaneous outgrowth of cells. The plating efficiency that may be crucial for clonal selection of transfected cells was negligible when dFb were plated without feeder cells at low density, while it was enhanced to 9-24% by the addition of a feeder layer of irradiated human embryonal fibroblasts. DFb secreted various cytokines with spontaneous release of interleukin-6 (IL-6) in high quantities of up to 20 ng/10(6) cells/24 hr. In addition, one-third of the culture secreted substantial amounts of granulocyte-macrophage colony-stimulating factor (GM-CSF), while low amounts of tumor necrosis factor-alpha (TNF-alpha) were detectable in some cases after irradiation of the cells. Comparison of various transfection methods by a transient luciferase expression assay demonstrated that receptor-mediated gene transfer was approximately 10-fold more efficient than cationic lipofection of dFb, while electroporation resulted in substantially less expression of the reporter gene. We conclude that primary dFb can be obtained reproducibly from human adults and represent a suitable target cell population for receptor-mediated gene transfer and cationic lipofection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Primary fibroblasts from human adults as target cells for ex vivo transfection and gene therapy. 784 93

Serum levels of 13 different cytokines and receptors were measured serially in 78 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by 4 cycles of an intensive multi-agent chemotherapy regimen. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously in 36 of these patients from day + 5 to day + 18 after each chemotherapy. Statistically significantly higher pretreatment levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), the soluble IL-2 receptor (sIL-2r), the soluble transferrin receptor (sTf-r), and neopterin, were observed in NHL patients as compared to controls (p < 0.001 for all molecules). sIL-2r and sTf-r levels correlated with tumor burden (p < 0.001 and p = 0.003, respectively) whereas IL-6 was higher in patients presenting B symptoms (p < 0.001). Cytokine levels progressively declined to normal ranges in responding patients, while they remained elevated in non-responders. Relapsed patients also presented increased concentrations of several molecules. During the administration of GM-CSF, we observed the drastic increase of sIL-2r, while lower elevations were recorded for a number of cytokines, including IL-8, tumor necrosis factor-alpha, interleukin-1 beta, IL-6, and IL-2. However, upon completion of the induction treatment, cytokine/receptor levels were comparable among individuals with the same type of response, whether or not they had received GM-CSF. No single parameter was found to be of prognostic significance, but the combination of elevated IL-10 and of sIL-2r greater than 3000 U/ml selected a subgroup of 7 patients who failed induction treatment (p = 0.002). These results demonstrate that cytokine and soluble receptor measurements can provide valuable informations for a better management of NHL, in terms both of markers to monitor disease activity and of prognostic indicators.
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PMID:Clinical implications of cytokine and soluble receptor measurements in patients with newly-diagnosed aggressive non-Hodgkin's lymphoma. 785 83

We have established a novel human megakaryoblastic cell line, designated as MEG-A2, from a patient with megakaryoblastic crisis of Philadelphia (Ph) chromosome positive chronic myelogenous leukemia. MEG-A2 cells showed positive phenotypes for periodic acid Schiff and alpha-naphthylbutyrate esterase reactions, but were negative for myeloperoxidase and naphthol ASD chloroacetate esterase reactions. Flow cytometric analyses of cell surface markers revealed that MEG-A2 cells had a low level of GP IIb/IIIa expression as well as apparent expressions of CD4, CD7, CD13, CD33 and CD34 antigens, but no expression of GP Ib nor glycophorin A. Stimulation with phorbol 12-myristate 13-acetate (PMA) dramatically increased the expression of megakaryocyte-related markers such as HPL-3, J15, Pit-1, Y2/51 and AN51 in MEG-A2 cells. The PMA-stimulation also induced expression of platelet peroxidase (PPO) in MEG-A2 cells on electromicroscopic observation. Proliferative responses to granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) or erythropoietin were observed, and the expression of GP IIb/IIIa was increased by stimulation with GM-CSF, IL-3, erythropoietin and interleukin-6 (IL-6). Protein S mRNA expression was seen in cultured cells on Northern blot analysis. Expression of platelet factor 4 mRNA was induced in PMA-stimulated cells, and a marked accumulation of protein was observed in the culture medium. In conclusion, a new cell line, MEG-A2, belongs to the relatively immature megakaryocytic lineage and has markedly increased megakaryocytic characteristics with PMA stimulation.
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PMID:Establishment and characterization of an immature human megakaryoblastic cell line, MEG-A2. 786 73

Cellular differentiation is thought to play an important role in the susceptibility of monocytic lineage cells to human immunodeficiency virus (HIV) infection as well as in their ability to support virus replication. In addition, virus replication in monocytes/macrophages has been demonstrated in vitro to be strongly modulated by several cytokines such as tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor. The purpose of the present study was to investigate the interaction between cellular differentiation and cytokines in the regulation of HIV expression from chronically infected monocytic lineage cells. U1, a persistently HIV-infected promonocytic cell line, is characterized by low levels of virus expression which can be modulated by several cytokines. 1 alpha,-25-Dihydroxyvitamin D3 (Vit.D3), a well-known differentiating agent for myelomonocytic cells which has been previously reported to modulate HIV replication in other in vitro systems, induced maturation of U1 cells toward a macrophage-like phenotype, as demonstrated by the induction of the differentiation-associated cell surface markers CD14 and CD11b. Vit.D3-induced differentiation did not result in induction of HIV expression; however, when U1 cells were stimulated with tumor necrosis factor alpha in the presence of Vit.D3, a synergistic induction of cell differentiation and viral expression was demonstrated. In contrast, Vit.D3 suppressed the induction of HIV expression in U1 cells stimulated with gamma interferon, interleukin-6, and granulocyte-macrophage colony-stimulating factor, although synergy between Vit.D3 and these cytokines was observed in terms of cellular differentiation. These data suggest that differentiation of monocytic cells does not necessarily correlate with increased HIV expression.
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PMID:Effect of cellular differentiation on cytokine-induced expression of human immunodeficiency virus in chronically infected promonocytic cells: dissociation of cellular differentiation and viral expression. 788 4

Serum levels of soluble intercellular adhesion molecule-1, soluble interleukin-2 receptor, and cytokines such as interleukin-3, interleukin-4, interleukin-6, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor were examined in patients with oral disorders with 20 healthy persons used as control subjects. Patients studied included 30 with squamous cell carcinoma, 26 with oral lichen planus, 20 with recurrent aphthous ulcer, 19 with acute odontogenic bacterial infection, 16 with pseudomembranous candidiasis, and 16 with herpetic gingivostomatitis. Compared with levels in control subjects, detectable serum levels of interleukin-3 (> or = 10 pg/ml) existed more frequently in pseudomembranous candidiasis (13/16), acute odontogenic bacterial infection (14/19), and squamous cell carcinoma (24/30) and of granulocyte-macrophage colony-stimulating factor (> or = 4 pg/ml) more frequently in recurrent aphthous ulcer (15/20) and squamous cell carcinoma (21/30). These cytokine levels were increased with T stage of squamous cell carcinoma. About 20 pg/ml of interleukin-4 was detected in serum from one third to one fourth of patients with oral lichen planus, recurrent aphthous ulcer, and squamous cell carcinoma. Tumor necrosis factor-alpha was hardly detected in most patients except those with oral lichen planus and squamous cell carcinoma in which about one third of the patients had more than 40 pg/ml of tumor necrosis factor-alpha in serum. More than 10 pg/ml of interleukin-6 was frequently detected in all disorders, especially recurrent aphthous ulcer (18/20), pseudomembranous candidiasis (12/16), and acute odontogenic bacterial infection (17/19).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum cytokines, interleukin-2 receptor, and soluble intercellular adhesion molecule-1 in oral disorders. 789 9

Recombinant human granulocyte-macrophage colony-stimulating factor therapy significantly reduces serum hepatitis B virus DNA levels, associated with increased 2',5'-oligoadenylate synthetase activity in cultured mononuclear cells of patients with chronic hepatitis B. To assess changes in immune function during therapy of chronic hepatitis B patients, spontaneous and mitogen-induced production of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interferon-alpha and interferon-gamma were measured-along with serum levels of soluble CD4, soluble CD8, soluble interleukin-2 receptor and beta 2-microglobulin-before, during and after a 6-wk course of granulocyte-macrophage colony-stimulating factor in nine patients with chronic hepatitis B. Treatment statistically enhanced spontaneous production of tumor necrosis factor-alpha (p < 0.05) and interleukin-1 beta (p < 0.02). Furthermore, spontaneous interleukin-6 production correlated negatively with hepatitis B virus DNA levels (p < 0.03), and spontaneous interleukin-1 beta production correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.0005). In addition, statistically significant increases were found during therapy in serum levels of soluble interleukin-2 receptor (p < 0.01), soluble CD4 (p < 0.01) and beta 2-microglobulin (p < 0.05). Levels of soluble interleukin-2 receptor and soluble CD4 correlated negatively with levels of hepatitis B virus DNA (p < 0.05), and levels of soluble interleukin-2 receptor and beta 2-microglobulin correlated positively with 2',5'-oligoadenylate synthetase activity (p < 0.003 and p < 0.02, respectively). Thus recombinant human granulocyte-macrophage colony-stimulating factor administration may induce reductions in hepatitis B virus DNA levels, perhaps by altering the immune status and increasing cytokine production.
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PMID:Changes in cytokine production during therapy with granulocyte-macrophage colony-stimulating factor in patients with chronic hepatitis B. 792 47

Myeloblasts derived from the peripheral blood of a patient with acute myelogenous leukemia (ORL47) were found to represent the malignant counterpart of the newly elucidated monocyte-dendritic cell colony-forming unit (mono-DC-CFU). The specific cytokine conditions require to achieve intermediate and terminal maturation of DCs and monocytes from these progenitors were defined. With tumor necrosis factor (TNF) + granulocyte-macrophage colony-stimulating factor (GM-CSF) + stem cell factor treatment numerous colony-like clusters developed. In contrast with normal DC development, further advancement of mono-DC-CFU and terminal DC maturation from the leukemic cells were dependent on the addition of interleukin-6. Functional and phenotypic analysis showed that the capacity to differentiate was maintained fully in the DC compartment, but only partially in the monocyte compartment, as judged by the lack of CD14 surface expression. Cells found at intermediate stages of DC development were potent stimulators of a mixed leukocyte reaction, a function usually attributed to mature DCs. As previously shown for normal DC development, antibodies to TNF alpha and GM-CSF blocked proliferative responses and DC growth. The importance of these observations in the classification of leukemias, normal DC development, and potential clinical strategies is discussed.
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PMID:Identification of a malignant counterpart of the monocyte-dendritic cell progenitor in an acute myeloid leukemia. 794 77

Serum levels of interleukin-1 (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured preoperatively in 24 patients with colorectal cancer. IL-1 beta was not elevated, IL-6 and IL-8 were markedly elevated, and GM-CSF was slightly elevated. TNF-alpha was not detected in most patients. Serum IL-6 levels correlated closely with serum IL-8 levels and with serum carbohydrate antigen (CA) 19-9 levels. Serum IL-6 levels were significantly higher in patients whose tumors exceeding 5.0 cm in diameter or spreading circumferentially. Serum IL-8 levels showed significant differences according to histological type, being lower in well differentiated adenocarcinoma compared to other types. Serum levels of IL-6 and IL-8 were significantly higher in patients with liver metastasis than in those without liver metastasis and serum levels of both these cytokines were also significantly higher in patients with lung metastasis than in those without lung metastasis. These results suggest that IL-6 and IL-8 may play an important role in the hematogenous metastasis of colorectal cancer.
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PMID:Serum levels of cytokines in patients with colorectal cancer: possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis. 795 51

To test the role of immune reactivity in the pathogenesis of hepatitis C, serum soluble immune factors were measured in a cohort of 57 patients with chronic hepatitis C, and in 20 healthy subjects. Levels of interleukin-1 beta, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-6 were detected in some, but not all, HCV patients and were in general undetectable in healthy subjects. Patients had significantly higher concentrations of neopterin (P = 0.0026), beta 2-microglobulin (P = 0.046), soluble interleukin-2 receptor (P = 0.021), and soluble CD8 (P < 0.039), than healthy controls; conversely, interferon-gamma levels were significantly lower (P = 0.023). Significant correlations were observed between beta 2-microglobulin concentration and Knodell's index (r = 0.638, P = 0.00045), the score of piecemeal necrosis (r = 0.572, P = 0.0023), and the degree of fibrosis (r = 0.527, P = 0.0056). Interleukin-2 levels correlated significantly with Knodell's index (r = 0.412, P = 0.037), and the degree of lobular cytolysis (r = 0.389, P = 0.048). According to therapeutic outcome, pretreatment levels of soluble CD8 were only significantly elevated (P = 0.042) in patients with a sustained biochemical response. On interferon-alpha treatment, the levels of beta 2-microglobulin, neopterin, and soluble interleukin-2 receptor increased significantly (P < 0.05), irrespective of therapy outcome. In summary, HCV patients have an altered immune reactivity that might play a role in the pathogenesis of chronic hepatitis C, and might influence the therapeutic outcome to interferon-gamma.
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PMID:Serum levels of soluble immune factors and pathogenesis of chronic hepatitis C, and their relation to therapeutic response to interferon-alpha. 795 20

When 15-deoxyspergualin (DSG) was administered into [BALB/c-->C3H/He] bone marrow (BM) chimeras from day 14 to day 25, increased platelet counts were observed from day 25 to day 33. Twofold increase of platelet counts was observed in DSG-treated BM chimeras compared with phosphate buffered saline (PBS)-treated BM chimeras. By using reverse transcriptase-polymerase chain reaction (RT-PCR), several cytokine mRNA expressions were analyzed in order to clarify which cytokines are involved in thrombopoiesis. So far, interleukin-6 (IL-6), leukemia inhibitory factor (LIF), stem cell factor (SCF), and IL-11 have been reported to have potent thrombopoietic activity in vivo. Although some other cytokines such as IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) possess the capacity of thrombopoiesis, megakaryocytopoiesis is more marked in these cytokines. IL-6 mRNA expression was increased in spleen cells from DSG-treated BM chimeras from day 25 to day 32 and in bone marrow cells from day 19 to day 28. LIF mRNA expression was not significantly increased compared with PBS control. Although SCF mRNA expression was increased, the kinetics of increased SCF mRNA expression did not fit the kinetics of increased platelet counts. Increased mRNA expression in other hematopoietic cytokines, such as IL-3, granulocyte-colony stimulating factor (G-CSF) and GM-CSF were also observed, thus suggesting that these cytokines may synergistically support thrombopoiesis in concert with IL-6. These results suggest that IL-6 and other hematopoietic cytokines might induce increased platelet counts, although the involvement of thrombopoietin (TPO) and IL-11 should be analyzed in the future.
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PMID:A novel immunosuppressant 15-deoxyspergualin and thrombopoiesis. 795 88

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