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)

HIV-specific cytotoxic T lymphocytes (CTLs) are an important component of the host immune response against HIV infection, and these cells release a variety of cytokines when they meet their target antigen. Since the phosphodiesterase inhibitor pentoxifylline is being used as a therapeutic agent in clinical trials of HIV infection due to its inhibitory effect on virus replication in vitro, we examined the effect of pentoxifylline on cytotoxicity and cytokine secretion by HIV-specific CD8+ CTLs. Pentoxifylline inhibited cytotoxicity of CTLs and suppressed interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor release by these cells at the transcription level. Suppression of cytokine release resulted in reduced capacity of the CTLs to induce HLA class I and ICAM-1 expression and to stimulate HIV-1 replication. These results suggest that inhibition of HIV-specific CD8+ CTLs by pentoxifylline may be therapeutically relevant. Moreover, this study extends previous observations by demonstrating that, in addition to its ability to suppress cytokine production by macrophages and CD4+ T helper cells, pentoxifylline may inhibit cytotoxicity and cytokine secretion by antigen-specific CD8+ cytotoxic T lymphocytes.
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PMID:Inhibition of cytotoxicity and cytokine release of CD8+ HIV-specific cytotoxic T lymphocytes by pentoxifylline. 758 37

Alterations in the ras p21 protein have been associated with both rodent and human neoplasia. Thus, mutated ras p21 proteins may bear unique antigenic epitopes for immune recognition, such as by T cells, which have been implicated in host antitumor activity. Synthetic peptides that mimic segments of mutated ras p21 have been reported to be immunogenic in mice in vivo, although detailed functional analyses remains undefined. Here, in a murine model, we explored and characterized distinct effector properties of host-derived T lymphocytes reactive to mutated ras peptides, which was consistent with the CD4+ T helper type 1 (Th1) subset. BALB/c mice (H-2d) were immunized with a purified peptide, 13 amino acids in length, containing the substitution of Gly (G12) to Val (V12) at position 12, which is commonly found in human carcinomas. An alpha beta T cell receptor-positive, CD3+, CD4+, CD8- T cell line was established, which expressed peptide-specific proliferation. Cytokine assays revealed the production of interleukin-2, interferon-gamma, tumor necrosis factor and granulocyte-macrophage colony-stimulating factor. Moreover, antigen-specific cytotoxicity was demonstrable against: (1) Iad-bearing A20 tumor cells incubated with exogenously bound V12 peptide; and (2) A20 tumor cells transduced with the K-ras p21 oncogene encoding the corresponding point mutation. CD4(+)-mediated cytotoxicity was major histocompatibility complex (MHC) class II-restricted, as revealed by the absence of lysis against MHC class II- P815 targets, inhibition of A20 lysis with anti-Iad monoclonal antibodies, and induction of lysis against L cell targets transfected with E alpha A beta d. Independent isolation of a second CD4+ V12 line revealed a very similar cytolytic and MHC class II-restricted profile. Overall, these data demonstrated that peptide immunization produced a CD4+ Th1 response that specifically recognized tumor cells expressing endogenous activated K-ras epitopes, which may have implications for the development of peptide-based active immunotherapies.
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PMID:Peptide-specific activation of cytolytic CD4+ T lymphocytes against tumor cells bearing mutated epitopes of K-ras p21. 758 31

Cytokine profiles of circulating mononuclear cells were studied with the aim of delineating T-cell subsets in leprosy patients with active disease. Using reverse transcriptase-polymerase chain reaction (RT-PCR) for cytokine mRNA and enzyme-linked immunoassay (ELISA) for the secreted products, interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were studied. Three antigens, native Mycobacterium leprae, a recombinant antigen LSR/A15 of M. leprae and peptide 624 spanning 58-77 amino acids of the latter, were used to induce cytokine expression and release. Half of the subjects, irrespective of the clinical type or antigen used, showed a mixed T-helper type 0 (Th0)-like cytokine pattern, with evidence of the concomitant presence of IFN-gamma and IL-4. The remainder showed a polarized pattern based on the type of leprosy. Lepromatous patients with disseminated disease had Th2-type cytokines, with IL-4 but not IFN-gamma. In contrast, tuberculoid leprosy patients with localized disease showed a Th1-like profile, with the presence of IFN-gamma but not IL-4. Of interest was the stability of the Th phenotype for M. leprae-related antigens. Both the recombinant and the peptide antigens induced the same phenotype as the natural M. leprae bacillus in all except four of 45 leprosy patients.
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PMID:Cytokine profile of circulating T cells of leprosy patients reflects both indiscriminate and polarized T-helper subsets: T-helper phenotype is stable and uninfluenced by related antigens of Mycobacterium leprae. 759 Aug 88

Treatment of murine bone marrow-derived macrophages with interferon-gamma (IFN-gamma) and/or lipopolysaccharide (LPS) resulted in changes in the abundance of a number of prenylated proteins. The most significant change involved a protein of 65 kd (p65) that became one of the most abundant prenylated proteins following treatment. The 65-kd protein was induced by agents that stimulate macrophage activation (IFNs or LPS) but not by cytokines that promote macrophage proliferation, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, or interleukin-3. The majority of p65 was localized to subcellular fractions containing internal and plasma membranes but was not detected in nuclear membranes. The farnesyltransferase inhibitor BZA-5B caused a dramatic decrease in p65 prenylation, suggesting that this protein may be modified by the C15 isoprenoid farnesyl. These observations provide the first direct evidence that interferons and LPS cause changes in the abundance of specific isoprenoid-modified proteins in macrophages.
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PMID:Induction of a prenylated 65-kd protein in macrophages by interferon or lipopolysaccharide. 759 63

Interleukin-12 (IL-12) is a monocyte/macrophage-derived cytokine that is critical for T lymphocyte and natural killer cell activities and functions. In this study, we examined the regulation of IL-12 expression by human monocytes in response to bacterial lipopolysaccharide (LPS). Several novel aspects of IL-12 induction from monocytes were shown. Optimal expression of IL-12 mRNA and bioactivity required specific priming of monocytes by interferon-gamma (IFN-gamma) before LPS stimulation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) provided an equivalent priming stimulus for LPS-induced tumor necrosis factor (TNF) and IL-12 p40 mRNA, but primed poorly for LPS-inducible p35 message and secreted IL-12 activity. Macrophage colony-stimulating factor (M-CSF), although a potent survival factor for monocytes, showed no priming activity for IL-12 production. Time course experiments demonstrated independent regulation of p40 and p35 by IFN-gamma and LPS. LPS inducibility of p40 expression required only a brief exposure to IFN-gamma (2 hours), while prolonged exposure (+/- 24 hours) to IFN-gamma resulted in diminishing levels of p40 mRNA. p35 inducibility (by LPS) required a longer exposure to IFN-gamma (8 to 16 hours), and continued to be inducible up to 40 hours following IFN-gamma priming. Both mRNAs were rapidly induced (1 to 2 hours) in IFN-gamma-primed monocytes; p35 message reached a plateau by 2 hours, while p40 continued to accumulate. Finally, both p40 and p35 were directly induced by LPS in the presence of cycloheximide. These results indicated that both p40 and p35 are LPS-inducible in monocytes following IFN-gamma pretreatment, and that the regulated expression of p35 controls the level of active IL-12 protein in purified human monocytes. The selectivity of priming by IFN-gamma is in accord with a putative role for IL-12 in the initiation and amplification of TH1-type responses.
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PMID:Regulation of interleukin-12 expression in human monocytes: selective priming by interferon-gamma of lipopolysaccharide-inducible p35 and p40 genes. 760 94

We investigated the significance of cytokines (soluble interleukin-2 receptor, granulocyte-macrophage colony-stimulating factor, interleukin-6, and interferon-gamma) and CD68-positive microparticles in immune thrombocytopenic purpura. Cytokines were measured by enzyme-linked immunosorbent assay and microparticles were detected by flow cytometry. CD68 expression by histiocytic U937 cells incubated with lipopolysaccharide or cytokines was also assessed in a control study. The level of CD68-positive microparticles was significantly higher in the patients with thrombocytopenia than in normal controls (p < 0.01). The soluble interleukin-2 receptor level was also significantly higher in patients than in controls (p < 0.01), but the other cytokines did not show a significant difference. However, patients with severe thrombocytopenia (platelet count > 20,000/microliters) had significantly higher levels of granulocyte-macrophage colony-stimulating factor and interleukin-6 than the controls (p < 0.05). When opsonized platelets were incubated with activated U937 cells, lipopolysaccharide and granulocyte-macrophage colony-stimulating factor caused an increase of CD68-positive microparticles in the supernatant. These results suggest that granulocyte-macrophage colony-stimulating factor is released by activated T cells in immune thrombocytopenic purpura and activates monocyte/macrophage phagocytosis, resulting in an increase of circulating CD68-positive microparticles and enhanced platelet destruction.
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PMID:Significance of cytokines and CD68-positive microparticles in immune thrombocytopenic purpura. 761 50

The V gamma 5/V delta 1(+)-T-cell receptor (TCR)-bearing T-cell clone, 2CBET-3, was generated from C57BL/6 mice. Upon stimulation, 2CBET-3 cells produce interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha, but not IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, macrophage colony-stimulating factor, or interferon-gamma. These cells were evaluated for their ability to be stimulated by a variety of murine cell lines, including fibroblasts, trophoblasts, melanoma cells, embryonic carcinomas, B-cell lymphomas, mastocytoma cells, and keratinocytes. The human B-lymphoma cell line, Daudi, also was included in these studies. We found that 2CBET-3 cells produced cytokines up to several hundredfold above the control levels in response to the B-cell lines, Daudi, and A20/2J, but not to the B-cell line 439.4.2. After fixation with glutaraldehyde, Daudi and A20/2J continued to stimulate this gamma delta T-cell line. 2CBET-3 cells also responded to the keratinocyte line PAM212, but not to another, XB-2. When lipopolysaccharides (LPS) from Escherichia coli or S. typhimurium were added to 2CBET-3 cells in the presence of A20/2J cells, 2CBET-3 cells responded with increased cytokine production compared with the cytokine production in the presence of A20/2J cells alone. 2CBET-3 cells by themselves did not respond to LPS alone or to supernatants from A20/2J cells incubated with LPS. Unlike 2CBET-3, the epidermal T-cell hybridoma 70BET-49, expressing a V gamma 5/V delta 1-TCR identical to that of 2CBET-3, did not respond to A20/2J cells in the presence or absence of LPS, suggesting a requirement for molecules other than the TCR for V gamma 5/V delta 1-TCR+ T-cell stimulation by the B-cell lines and by LPS. This unique reactivity of gamma delta-TCR+ cells is different from that of alpha beta-TCR+ cells and may reflect a functional specialization of gamma delta-TCR+ cells in the response to bacterial infections.
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PMID:Murine epidermal V gamma 5/V delta 1-T-cell receptor+ T cells respond to B-cell lines and lipopolysaccharides. 761 98

Immunization of BALB/c mice with human cartilage proteoglycan (aggrecan) produces a progressive polyarthritis, similar in many aspects to human rheumatoid arthritis, and autoreactive T cells are necessary for initiation of the disease. To study the immunopathological mechanisms operating in the synovium of arthritic mice, we isolated a proteoglycan (PG)-specific arthritogenic T-cell hybridoma, 5/4E8, and examined the presentation of PG to this T-cell hybridoma by mouse synovial cells and chondrocytes. Both cell types expressed very low levels of major histocompatibility complex (MHC) class II following isolation and culture and were unable to present PG to the hybridoma. However, following stimulation with interferon-gamma (IFN-gamma), both synovial cells and chondrocytes showed a marked increase in MHC class II expression and consequently were able to present PG very effectively. The PG-specific responses of the hybridoma were abrogated by an anti-Ia monoclonal antibody. Granulocyte-macrophage colony-stimulating factor (GM-CSF), one of the most abundant cytokines in the rheumatoid synovium, had no effect on the antigen-presenting capacity of synovial cells and chondrocytes, either on its own or together with IFN gamma.
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PMID:Interferon-gamma but not granulocyte/macrophage colony-stimulating factor augments proteoglycan presentation by synovial cells and chondrocytes to an autopathogenic T cell hybridoma. 762 93

Human natural killer cells (NK) respond to interleukin-2 (IL-2) with augmented cytolytic activity, cytokine secretion and cell proliferation. Here we show that IL-2 protects NK cells from death by apoptosis (programmed cell death; PCD). Highly purified NK cells (CD3- CD56+) were isolated from peripheral blood lymphocytes (PBL) of either control donors or of an asymptomatic donor with 60% NK cells. Glucocorticosteroids (GCS) induced PCD in NK cells, as shown by nuclear condensation and DNA fragmentation. IL-2 completely prevented GCS-induced PCD in a dose-dependent manner without overcoming GCS-induced inhibition of NK cell proliferation. The IL-2 protective effect was mediated through the p75 beta chain of the IL-2R, as neutralizing monoclonal antibody (mAb) to the p75 beta chain but not to the p55 alpha chain completely abolished the IL-2 anti-apoptotic activity. In addition to IL-2, the cytokines IL-7 and IL-12 have been reported to regulate NK cell functions. Our present data showed that IL-7 but not IL-12 rescued NK cells from apoptosis, but to a lesser extent than IL-2. Although IL-4 had a marginal protective effect, IL-1, IL-3, IL-6, IL-8, interferon-gamma (IFN-gamma) and IFN-alpha, tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and granulocyte-macrophage colony-stimulating factor (GM-CSF) displayed no significant activity. Finally, we report that IL-2 and IL-7 enhanced bcl-2 expression in NK cells, suggesting the existence of a bcl-2-dependent survival pathway. In addition to regulating various functions, it is concluded that IL-2 and IL-7 have the ability to prevent PCD in NK cells.
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PMID:IL-2 and IL-7 but not IL-12 protect natural killer cells from death by apoptosis and up-regulate bcl-2 expression. 764 25

The effects of 1 alpha,25-dihydroxyvitamin D3/calcitriol on the expression of Fc receptors (FcR) for IgA (Fc alpha R), IgE (Fc epsilon RII), and IgG (Fc gamma R) on human peripheral blood monocytes and the cell lines U937, THP-1, and Mono Mac-6, in combination with various cytokines, was examined by flow cytometry. On both monocyte-derived macrophages and the myelomonocytic cell lines, Fc alpha R/CD89 expression was induced by calcitriol alone and additively in combination with tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and granulocyte-macrophage colony-stimulating factor. Constitutive and interleukin-4 (IL-4)-driven Fc epsilon RII/CD23 expression was markedly diminished on calcitriol-treated U937 cells and monocytes. Fc epsilon RII was also triggered by IFN-gamma, TNF-alpha, and IL-6 on all the cell lines, an effect blocked by calcitriol. On monocytes, the basal level and IFN-gamma-induced Fc gamma RI/CD64 expression was down-regulated by calcitriol and IL-4. The expression of Fc gamma RII/CD32 on monocytes was strongly suppressed by calcitriol. Transforming growth factor-beta induced Fc gamma RIII/CD16 on monocytes, an effect opposed by calcitriol. The ability of calcitriol-treated monocytes to phagocytose IgG-sensitized ox erythrocytes was diminished. Our results demonstrate that calcitriol, alone or in combination with cytokines, modulates Fc alpha R, Fc epsilon RII, Fc gamma RI, and Fc gamma RII expression on human mononuclear phagocytes, as well as Fc gamma R-mediated phagocytosis.
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PMID:Modulation of IgA, IgE, and IgG Fc receptor expression on human mononuclear phagocytes by 1 alpha,25-dihydroxyvitamin D3 and cytokines. 764 18

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