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)

The ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) and 3'-azido-3'-deoxythymidine (AZT) to inhibit human immunodeficiency virus (HIV) in the U-937 monocytic cell line was examined. Acutely HIV-infected U-937 cells were exposed to GM-CSF (0.03, 0.3, 3.0, or 30.0 U/ml) and AZT (0.1, 1.0, or 10.0 microM) alone and in combination for 14 to 17 days. Reverse transcriptase activity in the supernatant, the percentage of cells expressing viral antigens by indirect immunofluorescence, and the 50% tissue culture infectious dose per milliliter of supernatant were determined to assess the level of viral replication in treated and control cultures. By the fractional-product method of analysis, nearly all combinations of GM-CSF and AZT synergistically inhibited HIV replication by these three measurements. The most effective combinations were 30 U of GM-CSF per ml with 0.1, 1.0, or 10.0 microM AZT. These treatments resulted in no reverse transcriptase activity in the supernatants, less than 1% immunofluorescent positive cells, and less than 8 50% tissue culture infectious doses per ml in the absence of cytotoxicity. Despite this degree of suppression, productive viral replication returned in all cultures within 4 to 10 days after drug removal. Combined therapy with GM-CSF and AZT merits consideration in the approach to HIV-associated illnesses.
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PMID:Synergistic activity of granulocyte-macrophage colony-stimulating factor and 3'-azido-3'-deoxythymidine against human immunodeficiency virus in vitro. 244 55

To extent our knowledge on the cytokines possibly involved in the pathophysiology of B-cell chronic lymphocytic leukemia (B-CLL), the mRNA expression of a panel of 10 cytokines was investigated on purified B-CLL cells using a reverse-transcriptase polymerase chain reaction method. Whereas negative RT-PCR signals were recorded for interleukin-1 alpha (IL-1 alpha), IL-2, IL-3, IL-4, IL-5, IL-7, tumor necrosis factor beta (TNF beta), and granulocyte-macrophage colony-stimulating factor, we detected the expression of IL-1 beta, IL-6 and TNF alpha. Furthermore, the constitutive expression of IL-8 mRNA was observed in all 17 B-CLL samples analyzed. mRNA expression was associated with the capacity of the leukemic cells to release IL-8 both constitutively (4.6 +/- 8.1 SD ng/mL) and, to a further extent, after stimulation (14.5 +/- 19.4 ng/mL). The circulating levels of IL-8 were also evaluated in 12 untreated B-CLL sera samples and the overall mean level was significantly higher (P < .01) than in normal sera. In addition, supernatants of purified B-CLL cells cultured in the presence of 12-O-tetradecanoylphorbol-13-acetate showed chemotactic activity towards neutrophils; this activity was neutralized in the presence of an anti-IL-8 antiserum. The mRNA for IL-8 was absent in five B-cell preparations from hairy cell leukemia cases and in four B-cell lines. Normal tonsil CD5+ B cells showed a low expression of IL-8 mRNA only in two of the nine preparations tested and the overall quantity of IL-8 released by these cells after 3 days' incubation was significantly lower compared with that released by B-CLL cells (0.4 +/- 0.3 and 1.6 +/- 0.9 ng/mL under basal and stimulated conditions, respectively). These findings point to an involvement of a member of the proinflammatory chemokine supergene family in human CD5+ B lymphocytes. The different IL-8 behavior observed between B-CLL cells and their normal counterpart is likely to reflect an activation state of the leukemic population.
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PMID:Cytokine gene expression in B-cell chronic lymphocytic leukemia: evidence of constitutive interleukin-8 (IL-8) mRNA expression and secretion of biologically active IL-8 protein. 751 9

In recent years, several studies have documented that melanoma cell lines produce various cytokine/growth factors and their receptors. Since cell lines can acquire altered properties, such as changes in growth requirements, we studied constitutive cytokine gene expression in melanoma cells from 20 fresh surgical specimens: seven primary melanomas and 13 metastases (12 lymph-node metastases and one subcutaneous metastasis). After tumour cell isolation by discontinuous gradient, we tested for mRNA expression by means of reverse-transcriptase polymerase chain reaction. Most melanoma cells tested expressed growth factors: basic fibroblast growth factor (bFGF), interleukin (IL)1 alpha, IL-1 beta, IL-6 and IL-8 and, in five cases out of 20, expressed granulocyte-macrophage colony-stimulating factor (GM-CSF) (two out of five were also positive for GM-CSF receptor). Our results do not point to a direct correlation between cytokine expression and clinical stage at the time when the bioptic specimen was obtained. However, they allow us to suggest a possible metastatic tumour cell phenotype, in which autogenous GM-CSF expression could modulate immune response against the tumour cell itself or could potentiate metastatic colonization properties.
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PMID:Cytokine expression in human primary and metastatic melanoma cells: analysis in fresh bioptic specimens. 773 55

Lymphohematopoiesis occurs in the densely packed environment of the intramedullary spaces. Primitive lymphohematopoietic stem cells exist in close apposition to a variety of supportive cells including both hemopoietic and nonhemopoietic lineages. Using an in vitro long-term Dexter liquid culture system, we have established that a variety of cytokines are produced constitutively by such stromal cells in culture. These cytokines include Steel factor, interleukin-6 (IL-6), and colony-stimulating factor (CSF-1). Granulocyte-CSF and granulocyte-macrophage-CSF mRNA can be detected after refeeding of cultures, although in quiescent cultures message for these factors is difficult to detect. Interleukin-3, IL-4, and IL-5 are not detectable by standard Northern blot analysis or bioassay of condition media. However, IL-3--detectable by reverse-transcriptase PCR and biologic activity--was confirmed by growth of factor-dependent cells on stromal cells with IL-3 antibody blocking of such growth. Stem cells resident on such stromal cells are mirrored by the high proliferative potential colony-forming cell assay and are responsive to a relatively large number of cytokines, with Steel factor being of central importance, appearing to be a critical component of various synergistic combinations. Steel factor allows reduced levels of other factors in such combinations and works early in a temporal sequence. Hematopoietic stem cells can engraft in normal nonmyeloablated hosts. Using a male/female BALB/c transplantation model, we have shown high rates of engraftment into normal animals, out after marrow infusion to 25 months, after marrow infusion and that post-5-fluorouracil bone marrow is quite deficient in such engraftment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro and in vivo studies of stromal niches. 799 65

Introduction of genes for cytokine receptors into hematopoietic stem/progenitor cells (HSC/HPC) may be of clinical use in the future. We recently reported that retroviral-mediated transduction of either the human erythropoietin receptor (hEpoR) or interleukin-9 receptor (hIL-9R) genes into highly purified HSC/HPC from cord blood (CB) resulted in increased numbers of detectable cytokine-responsive erythroid progenitors (burst-forming units-erythroid [BFU-E]). In the present study, we evaluated if this increase could be further enhanced by cotransducing both these genes into single isolated HSC/HPC. Single CD34++CD33-or low-expressing cells from CB were transduced with viral supernatant containing the hEpoR or hIL-9R genes or cotransduced with both genes. In the presence of Steel factor (SLF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (Epo), and IL-9, the numbers of erythroid colonies formed were significantly increased after transduction of cells with either the hIL-9R or hEpoR gene compared to mock-transduced cells. This increase was significantly enhanced in cells cotransduced with both genes compared with either gene alone. Integration and expression of both genes was confirmed by polymerase chain reaction (PCR) and reverse-transcriptase (RT)-PCR analysis, respectively. The data demonstrate that myeloid progenitors can be transduced at the single-cell level with both hEpoR and hIL-9R genes with resultant enhanced proliferation of these progenitors in the erythroid lineage by combinations of cytokines including Epo and IL-9.
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PMID:Influence of retroviral-mediated gene transduction of both the recombinant human erythropoietin receptor and interleukin-9 receptor genes into single CD34++CD33-or low cord blood cells on cytokine-stimulated erythroid colony formation. 864 64

Early hematopoietic progenitors expressing the CD34+ phenotype can be harvested from the peripheral blood of normal individuals. We have optimized the liquid culture of human CD34+ peripheral blood progenitors (PBPs) to achieve differentiation into a population of cells consisting almost entirely of eosinophil progenitors and maturing eosinophils. Growth of CD34+ PBPs for 28 days in the presence of the combination of IL-3, granulocyte-macrophage colony-stimulating factor, and IL-5 resulted in an almost 250-fold increase in cell number, yielding a population that contained 83% maturing eosinophils. The residual population consisted of basophils and mast cells (3% by acidic toluidine blue staining, 15.2% by flow cytometric assay for binding to high-affinity IgE receptor) and immature cells. This provides an opportunity to examine the kinetics of the acquisition of specialized mature eosinophil characteristics during eosinophil differentiation. Several host-defense and bioactive proteins are found almost exclusively in eosinophil granules. In addition, stimulated eosinophils, like neutrophils, produce copious amounts of toxic oxygen radicals. We used our culture system and the sensitive technique of reverse-transcriptase polymerase chain reaction to analyze the kinetics of production of messenger RNA transcripts encoding several eosinophil proteins, including five eosinophil granule proteins and four subunit peptides of the superoxide-generating reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in small numbers of differentiating eosinophils from peripheral blood CD34+ cells. Freshly isolated CD34+ PBPs contained transcripts for the ubiquitously present housekeeping protein phosphoglucokinase but contained no eosinophil granule protein transcripts and barely detectable amounts of some oxidase protein transcripts. On day 3 of culture, no cells recognizable by histochemical staining as eosinophils could be detected, but transcripts for all five eosinophil granule proteins were present. These transcripts increased several fold during the entire culture period. Similar kinetics were seen for all but one of the NADPH oxidase protein transcripts. However, transcripts for the p67phox NADPH oxidase protein were not detected until day 7, and functional oxidase activity did not appear until day 12. From that point, oxidase activity increased dramatically over the culture period. These studies demonstrate that commitment of CD34+ PBPs to the eosinophil lineage occurs very early, by day 3, but that further events in differentiation must take place before the appearance of histologically staining eosinophil granules and acquisition of functional oxidase capacity.
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PMID:Early commitment to the eosinophil lineage by cultured human peripheral blood CD34+ cells: messenger RNA analysis. 875 12

Multinucleated giant cells (MGC) are a hallmark of granulomatous reactions but the mechanisms that regulate their formation are unknown. To address this issue, we cultured resident alveolar macrophages (AM) from rat lung and examined the effects of defined cytokines on AM differentiation and MGC formation. The presence of MGC was found after 3 days in culture with maximal numbers obtained at 7 days and thereafter (up to 21 days). Macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (25-75 U/mL) stimulated the formation of MGC (up to 4-fold), whereas interleukin (IL) -3, IL-10, and interferon-gamma (IFN-gamma) had no stimulatory effect. Interestingly, MGC with distinct phenotypes were observed in AM cultures: (1) spherical MGC with 3-16 nuclei, dense cytoplasm, and lower expression of beta3 integrin (Type 1) and (2) irregular MGC with 3-30 nuclei, thin and vacuolated cytoplasm, and higher expression of beta3 integrin (Type 2). Furthermore, the actions of M-CSF and GM-CSF on AM were found to be different. GM-CSF promoted, in AM cultures, the appearance of an elongated fibroblastoid phenotype and stimulated mostly the formation of Type 2 MGC. In contrast, M-CSF did not cause significant change in the general morphology of regular AM but stimulated the appearance of both Type 1 and Type 2 MGC. Reverse transcriptase-polymerase chain reaction analysis demonstrated that, under these conditions, M-CSF induced GM-CSF gene expression in AM. In addition, neutralizing antibodies against M-CSF selectively decreased the formation of Type 1 MGC, whereas neutralizing anti-GM-CSF inhibited Type 2 formation. These data suggest that M-CSF promotes AM differentiation into Type 1 MGC, whereas GM-CSF stimulates the formation of Type 2 and that M-CSF and GM-CSF may selectively regulate in an autocrine fashion AM differentiation into distinct MGC.
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PMID:M-CSF and GM-CSF promote alveolar macrophage differentiation into multinucleated giant cells with distinct phenotypes. 886 36

Bronchial epithelial cells are primary sites of airway viral infection, and these cells may play an important role in the pathogenesis of respiratory diseases. It has recently been reported that bronchial epithelial cells express RANTES. RANTES attracts monocytes, T cells, eosinophils, and basophils; it can also activate eosinophils. To determine whether viral infection induces RANTES expression on bronchial epithelial cells, we infected a bronchial epithelial cell line, NCI-H292, with influenza virus A (H3N2). We then examined the concentration of RANTES in the culture medium of infected cells by ELISA and assessed expression of the gene for RANTES by the reverse-transcriptase polymerase chain reaction. We also investigated the concentrations of IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor in the medium of infected cells, because some virus infections have been reported to induce expression of these cytokines on bronchial epithelial cells, but there are few data concerning influenza virus infection. Small amounts of IL-6 and IL-8 were detected in the medium of uninfected cells. RANTES was not detected in the medium of uninfected cells. After influenza virus infection, significant amounts of IL-6, IL-8, and RANTES were released into the culture medium of infected cells, and RANTES messenger RNA was detected from infected cells. Granulocyte-macrophage colony-stimulating factor was not detected in the medium of uninfected and infected cells. These results suggest that influenza virus infection may stimulate production of IL-6, IL-8, and RANTES from human bronchial epithelial cells and that these cytokines may contribute to the pathogenesis of airway inflammatory diseases caused by influenza virus infection.
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PMID:Expression of IL-6, IL-8, and RANTES on human bronchial epithelial cells, NCI-H292, induced by influenza virus A. 897 9

Granulocyte-macrophage colony-stimulating factor, mobilized peripheral blood stem cell (PSC) products, and peripheral blood leukocytes posttransplantation contain cells that cause allogeneic and autologous T cell apoptosis. Isolation and characterization of these cells demonstrated that they were low-density (Percoll fractionation) CD14+ monocytes. T cells in PSC products have a depressed phytohemagglutinin (PHA) mitogenic response; however, purified CD4+ or CD8+ T cells exhibit a statistically normal mitogenic function. Furthermore, no T cell inhibitory activity was observed in CD14+, CD4+, and CD8+ cell-depleted fractions enriched in CD4- CD8- TCR alpha/beta+ T cells. Inhibition of T cell function by CD14+ monocytes required cell-cell contact, and the analyses of DNA fragmentation by Southern and TUNEL analysis demonstrates an activation-induced T cell apoptosis in the presence of CD14+ monocytes. Reverse-transcriptase polymerase chain reaction studies suggested that high levels of interleukin-10 or tumor necrosis factor gene transcripts in the PSC products may contribute to the inhibition of T cell function.
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PMID:Monocytes from mobilized stem cells inhibit T cell function. 912 7

The relative levels of selected cytokine, interleukin-2 receptor, class II DR and DQ RNAs, and maedi visna virus (MVV) RNA were measured by reverse-transcriptase polymerase chain reaction (RT-PCR) in the lungs of sheep with natural maedi visna virus infection (n = 8) and a group of age/sex/breed-matched MVV seronegative sheep (n = 4). These animals were divided into two groups, irrespective of serostatus, according to the severity of lymphocytic interstitial pneumonia. The severity of lung lesions was determined by clinical sign, lung weight, and lesion sore in the lungs measured by three pathologic parameters. Sheep with lung lesions showed hyperelevated levels of granulocyte-macrophage colony-stimulating factor upregulated gamma-interferon, interleukin 2 receptor, and interleukins 1 beta, 4, and 10 mRNAs. Class II mRNAs were found not to be elevated in the lungs of sheep with lung lesions. Tumor necrosis factor alpha and transforming growth factor beta 1 mRNA levels were similar in all sheep lungs studied. We discuss the major roles played by granulocyte-macrophage colony-stimulating factor and type 2 cytokines in the pathogenesis of this disease and the possible stimulation of the production of these cytokines by viral surface glycoproteins.
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PMID:Differential levels of mRNAs for cytokines, the interleukin-2 receptor and class II DR/DQ genes in ovine interstitial pneumonia induced by maedi visna virus infection. 916 76


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