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)

As is true for other intracellular pathogens, immunization with live Chlamydia trachomatis generally induces stronger protective immunity than does immunization with inactivated organism. To investigate the basis for such a difference, we studied immune responses in BALB/c mice immunized with viable or UV-killed C. trachomatis mouse pneumonitis (MoPn). Strong, acquired resistance to C. trachomatis infection was elicited by immunization with viable but not dead organisms. Immunization with viable organisms induced high levels of antigen-specific delayed-type hypersensitivity (DTH), gamma interferon production, and immunoglobulin A (IgA) responses. Immunization with inactivated MoPn mainly induced interleukin-10 (IL-10) production and IgG1 antibody without IgA or DTH responses. Analysis of local early cytokine and cellular events at days 3, 5, and 7 after peritoneal cavity immunization showed that high levels of granulocyte-macrophage colony-stimulating factor and IL-12 were detected with viable but not inactivated organisms. Furthermore, enrichment of a dendritic cell (DC)-like population was detected in the peritoneal cavity only among mice immunized with viable organisms. The results suggest that early differences in inducing proinflammatory cytokines and activation and differentiation of DCs may be the key mechanism underlying the difference between viable and inactivated organisms in inducing active immunity to C. trachomatis infection.
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PMID:Immunity to Chlamydia trachomatis mouse pneumonitis induced by vaccination with live organisms correlates with early granulocyte-macrophage colony-stimulating factor and interleukin-12 production and with dendritic cell-like maturation. 1008 93

In previous studies we characterized the cytokine regulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) secretion by endothelial cells and monocytes and found differences in secretion pattern within and between these cell systems. In this study, the regulatory effect of T lymphocytes on CSF secretion was examined. T lymphocytes had no effect on CSF secretion by endothelial cells. In contrast, the addition of T lymphocytes significantly and dose dependently downregulated GM-CSF, but not G-CSF, secretion by monocytes. In one of our previous studies it was shown that interleukin-4 (IL-4) and interleukin-10 (IL-10) were the most potent inhibitory cytokines of CSF secretion by monocytes. Both these cytokines are produced by T lymphocytes. However, the downregulating effect on monocyte GM-CSF secretion was not due to increased secretion of T-lymphocyte-derived IL-4 or IL-10. Instead, the presence of T lymphocytes increased the secretion of monocyte-derived IL-10. It was shown earlier than IL-10 regulates CSF secretion by monocytes in an autocrine manner. Our data indicate that T lymphocytes might interfere with this autocrine regulation and thereby influence monocyte function in immune response and cell proliferation.
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PMID:T lymphocytes downregulate granulocyte-macrophage colony-stimulating factor secretion from stimulated monocytes by increasing the secretion of monocyte-derived interleukin-10. 1008 2

In the present study, we have investigated the effects of interferons-alpha (IFN-alpha) and -gamma (IFN-gamma), interleukin-10 (IL-10) and -13 (IL-13), transforming growth factor-beta1 (TGF-beta1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha) on cell proliferation and induction of transcription factors AP-1 and NF-kappaB in UM-EC-3 human endometrial adenocarcinoma cells and UT-OC-5 ovarian carcinoma cells in vitro. In addition, cellular DNA was extracted to study if any of these factors is able to induce apoptosis. In UM-EC-3 cell line DNA synthesis was inhibited by GM-CSF, IL-10, IL-13, TGF-beta1, IFN-alpha, and IFN-gamma after 48 and 72 h in culture, whereas TNF-alpha had no significant effect on cell proliferation in any of the experiments. The inhibition of DNA synthesis was similarly observed in UT-OC-5 ovarian carcinoma cells by IL-10, TNF-alpha, and IFN-gamma after 48 and 72 h, whereas IFN-alpha had no statistically significant effect. An inhibitory effect of GM-CSF was observed only after 48 h and TGF-beta after 72 h in culture, respectively. Transcription factors AP-1 and NF-kappaB were both constitutively active in UM-EC-3 and UT-OC-5 cells. The binding activity of AP-1 was found to be stimulated by all growth-inhibitory cytokines studied in both cell lines, whereas the specific binding activity of NF-kappaB was affected moderately only by TNF-alpha in UT-OC-5 ovarian carcinoma cells. No signs of DNA fragmentation typical of apoptosis were observed in any of these studies.
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PMID:Inhibitory effects of cytokines on ovarian and endometrial carcinoma cells in vitro with special reference to induction of specific transcriptional regulators. 1036 39

Sargramostim is a yeast-derived, recombinant human granulocyte-macrophage colony-stimulating factor with therapeutic potential in human immunodeficiency virus (HIV) infection. Its safety and activity when used in combination with protease inhibitors were evaluated in a randomized, double-blind trial in which 20 HIV-infected subjects on stable antiretroviral regimens, including indinavir or ritonavir, received sargramostim or placebo 3 times a week for 8 weeks. Analysis of HIV virus load excluded any 0. 5 log10 increase due to sargramostim (95% confidence interval, -0.68 to 0.44). Sargramostim was well tolerated, and inflammatory cytokines and surrogate markers of disease progression, such as serum levels of interleukin-10 and soluble tumor necrosis factor receptors types Iota and IotaIota, remained stable in subjects receiving sargramostim. Sargramostim treatment was associated with a trend toward decreased HIV RNA (>0.5 log10) and increased CD4+ cell count (>30%). These results became statistically significant only when subjects with baseline virus loads within the limits of detection or baseline CD4 cell count >50 were analyzed. No difference in indinavir pharmacokinetics was observed before or after sargramostim therapy.
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PMID:The safety and efficacy of granulocyte-macrophage colony-stimulating factor (Sargramostim) added to indinavir- or ritonavir-based antiretroviral therapy: a randomized double-blind, placebo-controlled trial. 1047 32

In vivo, dendritic cells (DC) form a network comprising different populations. In particular, Langerhans cells (LC) appear as a unique population of cells dependent on transforming growth factor beta(TGF-beta) for its development. In this study, we show that endogenous TGF-beta is required for the development of both LC and non-LC DC from CD34+ hematopoietic progenitor cells (HPC) through induction of DC progenitor proliferation and of CD1a+ and CD14+ DC precursor differentiation. We further demonstrate that addition of exogenous TGF-beta polarized the differentiation of CD34+ HPC toward LC through induction of differentiation of CD14+ DC precursors into E-cadherin+, Lag+CD68-, and Factor XIIIa-LC, displaying typical Birbeck granules. LC generated from CD34+ HPC in the presence of exogenous TGF-beta displayed overlapping functions with CD1a+ precursor-derived DC. In particular, unlike CD14(+)-derived DC obtained in the absence of TGF-beta, they neither secreted interleukin-10 (IL-10) on CD40 triggering nor stimulated the differentiation of CD40-activated naive B cells. Finally, IL-4, when combined with granulocyte-macrophage colony-stimulating factor (GM-CSF), induced TGF-beta-independent development of non-LC DC from CD34+ HPC. Similarly, the development of DC from monocytes with GM-CSF and IL-4 was TGF-beta independent. Collectively these results show that TGF-beta polarized CD34+ HPC differentiation toward LC, whereas IL-4 induced non-LC DC development independently of TGF-beta.
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PMID:Respective involvement of TGF-beta and IL-4 in the development of Langerhans cells and non-Langerhans dendritic cells from CD34+ progenitors. 1057 10

The down regulation of CD4 by cultured monocytes has been observed by our group and by other investigators. Flow cytometric experiments were done to examine which factors might influence this phenomenon. The addition of lipopolysaccharide, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, or interleukin-10 to monocyte cultures failed to inhibit the decrease in monocyte CD4 expression routinely observed following overnight culture. The down regulation was an adherence-independent phenomenon and was not influenced by the type of anticoagulant into which the peripheral blood was collected or by the presence or absence of lymphocytes within the cultures. The avoidance of the use of Ficoll-Paque to isolate peripheral blood mononuclear cells did not prevent monocyte CD4 down regulation. Finally, by tagging monocyte CD4 with an anti-CD4 phycoerythrin-conjugated monoclonal antibody prior to culture, we were able to determine that the down regulation observed was the result of the internalization of the molecule. At this time, we conclude that the observed down regulation of monocyte CD4 is probably due to the differentiation of blood monocytes into tissue culture-derived macrophages rather than to some artifact of the isolation procedure.
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PMID:Down regulation of CD4 expression following isolation and culture of human monocytes. 1070 90

The present study was designed to ascertain whether or not the pleural effusion and serum cytokine levels (granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin-10 [IL-10], and interferon-gamma [IFN gamma]) in lung cancer patients differ from tuberculous (TB) pleural effusion, in which a strong cellular immune reaction is found; and, whether cytokine levels are a prognostic factor in lung cancer patients with malignant effusion. A total of 202 lung cancer patients with malignant pleural effusion and 26 patients with TB pleural effusion were studied consecutively between 1995 and 1998. Serum and effusion cytokine levels were analyzed with ELISA assays. The results showed that pleural effusion GM-CSF and IL-10 levels were significantly higher than serum levels in both cancer and TB patients. Pleural effusion IFN gamma levels were significantly higher than serum levels in TB patients. IFN gamma levels in both pleural effusion and serum were significantly higher in TB patients than in those with cancer. No significant difference was found, between TB and cancer patients, in the serum or pleural effusion levels of either IL-10 or GM-CSF. The ratio of pleural effusion IFN gamma to serum IFN gamma, effusion IFN gamma to effusion IL-10, and effusion IL-10 to serum IL-10, were all significantly higher in TB than in cancer patients, suggesting a higher cellular activity and T-helper 1 (Th1) reaction in TB pleural effusion than in malignant effusions, which were predominantly Th2 type. Survival analysis showed no significant difference in lung cancer patients with different levels of these cytokines. It was concluded that lung cancer patients with malignant pleural effusion had poorer immune profiles than those with TB pleurisy, both locally and systemically; and the cytokine profiles were not prognostic factors for lung cancer patients with malignant pleural effusion.
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PMID:An analysis of cytokine status in the serum and effusions of patients with tuberculous and lung cancer. 1116 63

B7-H1 is a recently described B7-like molecule that costimulates T-cell growth and cytokine secretion without binding to CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4), and inducible costimulator (ICOS). In this report, a mouse homologue of human B7-H1 is identified, and its immunologic functions are studied in vitro and in vivo. Mouse B7-H1 shares 69% amino acid homology to the human counterpart. Similar to human B7-H1, mouse B7-H1 can be induced to express on macrophages, T cells, and B cells and to enhance T-cell proliferation and secretion of interleukin-10 (IL-10), interferon-gamma, and granulocyte-macrophage colony-stimulating factor but not IL-2 and IL-4. Furthermore, B7-H1 preferentially costimulates CD4+ T cells independently of CD28 and enhances mixed lymphocyte responses to allogeneic antigens. In contrast to B7-1, expression of B7-H1 on murine P815 tumor cells by transfection fails to increase allogeneic and syngeneic cytolytic T-cell responses in vitro and in vivo. Administration of B7-H1Ig fusion protein, however, enhances keyhole limpet hemocyanin- specific T-cell proliferation and 2,4,6-trinitrophenyl-specific immunoglobulin G2a antibody production. The study thus identifies a unique costimulatory pathway that preferentially affects T-helper cell functions.
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PMID:B7-H1 costimulation preferentially enhances CD28-independent T-helper cell function. 1123 24

We previously reported that immunization with H antigen from Histoplasma capsulatum did not protect mice against an intravenous challenge with yeasts. Here, we investigated the utility of H antigen to protect mice in a model of pulmonary histoplasmosis. Mice immunized with H antigen and challenged intranasally 4 weeks postvaccination were protected against sublethal and lethal challenges with H. capsulatum yeasts. If the challenge was performed 3 months after vaccination, there was a reduction in fungal burden following sublethal challenge and a modest delay in mortality in mice given a lethal inoculum. Vaccination was associated with production of gamma interferon, granulocyte-macrophage colony-stimulating factor, interleukin-4, and interleukin-10 by splenocytes. Vaccination with H antigen was not accompanied by a major expansion of CD4(+) or CD8(+) cells in spleens of mice. These results demonstrate that H antigen may be useful as a protective immunogen against pulmonary exposure to H. capsulatum.
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PMID:Protective efficacy of H antigen from Histoplasma capsulatum in a murine model of pulmonary histoplasmosis. 1129 32

On an island in which bancroftian filariasis is endemic, 29 microfilaremic and 16 "endemic normal" (EN) subjects initially studied in 1974-1975 were reevaluated 17 years later. Eleven persons remained microfilaremic, whereas 18 had cleared both microfilaremia and antigenemia. Despite decreased infection on the island, antibody levels remained relatively constant for the subjects with persistent microfilaremia (Mf(+/+)), in contrast to sharp decreases for both EN subjects and subjects with cleared microfilaremia (Mf(+/-)). Although clinically indistinguishable from the EN subjects, the Mf(+/-) group had antibody levels (IgG, IgG4, and IgE) significantly lower than those of the EN subjects. Lymphocyte responses to parasite antigens were marginally greater in Mf(+/-) than in Mf(+/+) subjects, but both groups remained less cell responsive (as measured by proliferation, interleukin-5, interleukin-10, interferon-gamma, and granulocyte-macrophage colony-stimulating factor) than did the EN subjects. These findings suggest that, for microfilaremic persons, complete clearance of infection is not sufficient to restore "normal" immune responsiveness; filarial infection may induce very long-term deficits in the ability to respond to parasite antigens.
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PMID:Evolution of immunologic responsiveness of persons living in an area of endemic bancroftian filariasis: a 17-year follow-up. 1139 12


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