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)

HLA class I and II molecules play a central role in regulating host immune responses against microbial infections because they present foreign antigens to CD8+ and CD4+ T lymphocytes, respectively. Many cytokines, especially interferons (IFN), are known to upregulate human leucocyte antigen (HLA) class I and II gene expression, but the kinetics, expression levels and viral regulation of HLA genes in primary human cells have not been well documented. Stimulation of peripheral blood mononuclear cells (PBMC) with IFN-alpha and IFN-gamma resulted in a 1.5- to twofold increase in HLA class I and beta 2-microglobulin expression in lymphocytes and monocytes. Lymphocytes did not express any detectable HLA class II either basally or after IFN induction. In monocytes, instead, a high basal class II expression was found and it was further induced by IFN-alpha (up to twofold) and especially by IFN-gamma (up to fivefold). In granulocyte-macrophage colony-stimulating factor (GM-CSF) differentiated human macrophages, basal HLA class I and II protein expression levels were high but IFN-gamma stimulation was able to further enhance their expression. Accordingly, class I and II mRNA expression was elevated by IFN-gamma, whereas IFN-alpha practically had no effect on HLA class I mRNA levels. Influenza A virus infection of macrophages resulted in temporary increases in HLA class I, beta 2-microglobulin and class II antigen expression. Neutralization of virus-induced IFN production by antibodies against type I and II IFNs prevented the virus-induced upregulation of HLA antigens. At late times of infection, as analysed by steady-state mRNA expression, both HLA class I and II mRNA were strongly reduced. These results suggest that IFNs are important regulators of HLA genes and responsible for a temporary increase in HLA antigen expression during influenza A virus infection.
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PMID:Regulation of HLA class I and II expression by interferons and influenza A virus in human peripheral blood mononuclear cells. 930 32

Human T-cell leukemia virus type-I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL) transforms human T cells both in vivo and in vitro. However, the long latency period between infection and development of ATL, as well as the small fraction of the infected population that actually develops this disease, suggest that factors in addition to the virus are involved in its pathogenesis. Mutation of tumor suppressor gene p53 has been found in both HTLV-I-transformed T-cell lines and ATL cases at relatively low frequency. However, increasing evidence supports p53 functional impairment in HTLV-I-transformed T cells. Tax, the major transactivator of HTLV-I, is critical for the initial events involved in transformation. We have considered the possibility that p53 may regulate transcription of viral and cellular genes important for viral replication and transformation. Inactivation of p53 function might then permit constitutive expression of these viral and cellular genes. We have investigated the effects of wild-type and mutant p53 on Tax-mediated activation of the HTLV-I long terminal repeat (LTR) and the promoters of several cellular genes including the interleukin (IL)-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF ), and IL-2 receptor alpha chain gene. Jurkat, HuT78, and U937 cells were cotransfected with plasmids containing a chloramphenicol acetyltransferase (CAT ) reporter gene under viral or cellular promoter control and the Tax expression vector, in addition to vectors for a wild-type or mutant p53. Wild-type p53 is a potent repressor of viral and cellular activation by Tax. Mutations within p53 severely inhibit this downregulation. We also show that wild-type p53 suppresses transcription from the HTLV-I LTR in Jurkat-Tax, a T-cell line stably expressing Tax, and MT-2, a HTLV-I-transformed T-cell line. Wild-type, but not mutant, p53 interfered with the binding of TATA-binding protein (TBP) to the TATA motif of the HTLV-I LTR. These results suggest that p53 inactivation may lead to upregulation of viral and cellular genes and may also be important for establishment of productive viral infection and development of ATL.
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PMID:Repression of transcription from the human T-cell leukemia virus type I long terminal repeat and cellular gene promoters by wild-type p53. 938 10

Orf virus is an epitheliotropic DNA parapoxvirus with a worldwide distribution that induces acute pustular lesions in the skin of sheep, goats and man. Genetic mapping and sequencing of the orf virus genome have revealed that orf virus has a typical poxvirus distribution of genes, with those essential for viral DNA synthesis, replication and packaging located in the central region, and those involved in virulence concentrated in the terminal regions. The immune and inflammatory response to orf virus infection in the skin and local lymph is vigorous and typical of an anti-viral response, involving CD4+ helper and CD8+ cytotoxic T cells, interferons and antibodies. In spite of this, the virus can repeatedly infect sheep. Host acquired immunity involving CD4+ T cells and interferons is effective in controlling the extent of viral replication, but does not prevent reinfection. Several virus putative virulence genes have been identified. These are: viral homologues of ovine vascular endothelial growth factor (VEGF); ovine IL-10; vaccinia virus E3L interferon resistance gene; and in addition a viral activity that inhibits the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). These may be responsible for rescuing orf virus, at least temporarily, from host immunity and aiding viral replication in epidermal cells.
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PMID:Ovine diseases. Orf. 968 44

CCR5 and CXCR4 are the major HIV-1 coreceptors for R5 and X4 HIV-1 strains, respectively, and a threshold number of CD4 and chemokine receptor molecules is required to support virus infection. Therefore, we used a quantitative fluorescence-activated cell sorting assay to determine the number of CD4, CCR5, and CXCR4 antibody-binding sites (ABS) on various T cell lines, T cell subsets, peripheral blood dendritic cells (PBDC), and monocyte-derived macrophages by using four-color fluorescence-activated cell sorting analysis on fresh whole blood. Receptor levels varied dramatically among the various subsets examined and typically varied from 2- to 5-fold between individuals. CCR5 was expressed at much higher levels in CD4+/CD45RO+/CD62L-true memory cells compared with CD4+/CD45RO+/CD62L+ cells. Fresh PBDC had the highest number of CCR5 ABS among the leukocyte subsets examined but had few CXCR4 ABS, affording a strategy for sort-purifying PBDC. In vitro maturation of PBDC resulted in median 3- and 41-fold increases in CCR5 and CXCR4 ABS, respectively. We found that macrophage colony-stimulating factor caused the greatest up-regulation of both CCR5 and CXCR4 on macrophage maturation (from approximately 5,000 to approximately 50, 000 ABS) whereas granulocyte-macrophage colony-stimulating factor caused a marked decrease of CXCR4 (from approximately 5,000 ABS to <500) while up-regulating CCR5 expression (from approximately 5,000 to approximately 20,000 ABS). Absolute ABS for CD4 and the major HIV-1 coreceptors serve as a more quantitative measure of cell surface expression, and we propose that this be used for future studies looking at the modulation of CD4 or chemokine receptor expression by cytokines, HIV-1 infection, or receptor polymorphisms.
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PMID:Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. 1022 Apr 46

There is increasing evidence that the asthma process is 'driven' and maintained by persistence of a subset of chronically activated T memory cells, sensitized against allergenic, occupational or viral antigens which 'home' to the lung after antigen exposure or viral infection. In general, allergens induce a CD4 T helper (Th) cell response, whereas viruses recognize CD8+ cytotoxic (Tc) T cells. In the asthmatic airways, there are CD4+ and, to a lesser number CD8+ cells with a type 2 cytokine phenotype (i.e., Th-2 and Tc-2 type). These cells produce interleukin (IL) 3 and 5 and granulocyte-macrophage colony-stimulating factor which recruit, mobilize and activate eosinophils for subsequent mucosal damage, as well as IL-4, an essential cofactor for local or generalized IgE production. This leads to epithelial shedding, mucus hypersecretion and bronchial muscle contraction. Thus, although the eosinophil may damage the mucosal surfaces in asthma, its function appears to be under T cell control. Support for this hypothesis includes: (1) activated T cells and their products can be identified in biopsies from the major variants of the disease (atopic, non-atopic and occupational asthma); (2) colocalization of mRNA for type 2 cytokines to CD4+ and CD8+ cells in atopic and non-atopic asthma; (3) the presence of activated cytokine-producing T cells in corticosteroid-resistant asthma; (4) the association of disease severity with type 2 cytokines, especially IL-5; and (5) the efficacy of cyclosporin A and a monoclonal anti-CD4 in chronic steroid-dependent disease. Inhibitors and/or antagonists directed against more precise T cell associated molecular targets hold promise for the future treatment of chronic asthma.
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PMID:T cells and chronic asthma. 1022 60

To further understand the early biochemical events that occur in infected surface epithelium, we developed for the first time a model in which a respiratory submucosal gland cell population can be infected with rhinovirus (RV). Viral infection was confirmed by demonstrating with PCR that viral titers in supernatants and lysates from infected cells increased with time. Infection by RV14 upregulated the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA, the major RV receptor, on submucosal gland cells, and it increased production of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor in supernatants. Antibodies to ICAM-1 inhibited RV infection of submucosal gland cells and decreased the production of cytokines after RV infection. Both IL-1alpha and IL-1beta upregulated ICAM-1 mRNA expression and increased susceptibility to RV infection, whereas other cytokines failed to alter ICAM-1 mRNA expression. Furthermore, neutralizing antibodies to IL-1alpha and IL-1beta significantly decreased the viral titers in supernatants and ICAM-1 mRNA expression after RV infection, but a neutralizing antibody to tumor necrosis factor-alpha was without effect. These findings suggest that respiratory submucosal gland cells play an important role in the initial stages of inflammation and provide useful insights into the pathogenesis of RV infection.
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PMID:Infection of human respiratory submucosal glands with rhinovirus: effects on cytokine and ICAM-1 production. 1044 31

The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the differentiation of dendritic cells (DCs) during pulmonary viral infection was investigated by using a mouse model of GM-CSF transgene expression established with an adenoviral vector (AdGM-CSF). GM-CSF gene transfer resulted in increased levels of GM-CSF in the lung, which peaked at day 4 and remained increased up to day 19. A striking cellular response composed predominantly of macrophage-like cells was observed in the lung receiving AdGM-CSF but not control vector. By FACS analysis, the majority of these cells were identified at an early time point as macrophages and later as mature/activated myeloid DCs characterized by CD11b(bright), CD11c(bright), MHC class II(bright), and B7.1(bright). In contrast, GM-CSF had a weak effect on a small DC population that was found present in normal lung and was characterized by CD11c(bright) and CD11b(low). By immunohistochemistry staining for MHC II, the majority of activated antigen-presenting cells were localized to the airway epithelium and peribronchial/perivascular areas in the lung. A concurrently enhanced Th1 immune response was observed under these conditions. The number of CD4 and CD8 T cells was markedly increased in the lung expressing GM-CSF, accompanied by increased release of interferon (IFN)gamma in the lung. Furthermore, lymphocytes isolated from either lung parenchyma or local draining lymph nodes of these mice but not the control mice released large amounts of IFNgamma on adenoviral antigen stimulation in vitro. These findings reveal that GM-CSF promotes the differentiation and activation of a myeloid DC population primarily by acting on macrophages during pulmonary immune responses.
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PMID:Transgenic expression of granulocyte-macrophage colony-stimulating factor induces the differentiation and activation of a novel dendritic cell population in the lung. 1073 4

Cytokines and chemokines play important roles in both autoimmune and infectious arthritides. Here we describe the cytokines and chemokines induced by Ross River (RR) virus infection of synovial fibroblasts and macrophages in vitro. RR virus is the aetiological agent of epidemic polyarthritis (EPA), a principally acute and chronic rheumatic disease affecting up to 7,000 Australians annually. Infected fibroblasts increased expression of mRNA coding for monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor. MCP-1, IL-8, macrophage inflammatory protein-2, and to a lesser extent interferon gamma-induced protein-10 mRNA were upregulated in infected macrophages. Expression of MCP-1 is consistent with the predominantly monocytic effusion found in EPA synovia.
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PMID:An arthrogenic alphavirus induces monocyte chemoattractant protein-1 and interleukin-8. 1077 38

We report here the first demonstration of dengue virus infection and vasoactive cytokine response of a cell of the mast cell/basophil lineage. Infection of KU812 cells was dependent on dengue-specific antibody and gave rise to infectious virions. This antibody-enhanced dengue virus infection triggered a four- to fivefold increase in the release of interleukin-1beta (IL-1beta) and a modest increase for IL-6 but not for an alternate cytokine, granulocyte-macrophage colony-stimulating factor. The results suggest a potential role for mast cells/basophils in the pathogenesis of dengue virus-induced disease.
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PMID:Release of vasoactive cytokines by antibody-enhanced dengue virus infection of a human mast cell/basophil line. 1088 55

Many nasopharyngeal carcinoma (NPC) biopsy specimens contain Epstein-Barr virus (EBV). However, the response of NPC cells to EBV infection in vitro and in vivo is not well characterized. In this experiment we infected NPC cells with EBV particles through endocytosis of a complex of EBV immunoglobulin A (IgA) secretory component (SC) protein to observe the response of host cells to the foreign viral infection in vitro. We found that EBV particles were endocytosed and stabilized in NPC nuclei 24 hours after infection; the EBV genomes were then gradually decreased after serial passages within 3 to 4 weeks by the following pathway: the EBV genomes first moved toward the nuclear envelope from the center of the nucleus; after crossing the nuclear envelope, they moved into the cytoplasm and toward the plasma membrane and were discharged by exocytosis. At the 10th day of EBV infection, EBV-latent membrane protein-1 and Epstein-Barr nuclear antigen (EBNA)-1 protein expressions could be detected, but not EBV-viral capsid antigen. Observation of EBNA-1 protein and host growth factor and cytokine gene expressions in the weeks after incubation revealed that the EBNA-1 protein expression was decreased proportionally with decrease of EBV genome. The mRNA expression of epithelial growth factor receptor, transforming growth factor (TGF)-alpha, interleukin (IL)-1beta, IL-6, and granulocyte-macrophage colony-stimulating factor increased within 1 to 2 weeks after infection, and gradually recovered to the original level at 3 to 4 weeks, whereas the mRNAs of TGFbeta1, TGFbeta receptor type I (TGFbetaRI), TGFbetaR type II, IL-8, and tumor necrosis factor-alpha remained unchanged. It is concluded that in vitro EBV infection in NPC cells results in increase of certain growth factor and cytokine gene expressions in host cells. The change in gene expression returns to the original level approximately 3 to 4 weeks after infection because of exocytosis of EBV DNA by the infected cells through an unidentified mechanism.
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PMID:Response of nasopharyngeal carcinoma cells to Epstein-Barr virus infection in vitro. 1095 Jan 6


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