The Experts below are selected from a list of 25629 Experts worldwide ranked by ideXlab platform

G Herbein - One of the best experts on this subject based on the ideXlab platform.

  • hiv 1 induces tumour necrosis factor and il 1 gene expression in Primary human macrophages independent of productive infection
    Clinical and Experimental Immunology, 2008
    Co-Authors: G Herbein, Satish Keshav, Matthew Collin, Luis J Montaner, Siamon Gordon
    Abstract:

    Cytokines such as tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta may play a role in immunopathogenesis of AIDS. We studied early effects (0.5-48 h) of monocytotropic (ADA) or lymphotropic (IIIB) strains of HIV-1 on TNF-alpha and IL-1 beta mRNA expression in Primary human macrophages by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Three-day-old monocyte-derived macrophages were exposed either to Tissue Culture supernatants containing virus (at multiplicity of infection (m.o.i.) of 0.05) or to control supernatants free of virions and gp120. ADA strain, but not IIIB, replicated in Primary Tissue Culture-differentiated macrophages (TCDM). Soluble CD4 (sCD4) was used to inhibit binding of both strains to macrophages. We found that TNF-alpha and IL-1 beta gene expression was induced by both strains 0.5-3 h after addition of virus, and that enhanced expression of both cytokines was inhibited by sCD4. We conclude that CD4-dependent binding to the cell surface is sufficient to enhance TNF-alpha and IL-1 beta mRNA, whereas productive viral replication in Primary human macrophages is not required. Therefore, similar pathways regulate gene expression of TNF-alpha and IL-1 beta by macrophages during initial infection by HIV-1 in vitro.

  • hiv 1 envelope glycoprotein gp120 down regulates cd4 expression in Primary human macrophages through induction of endogenous tumour necrosis factor alpha
    Immunology, 1996
    Co-Authors: V Karsten, Siamon Gordon, A Kirn, G Herbein
    Abstract:

    Among immunological abnormalities present in human immunodeficiency virus type 1 (HIV-1)-infected individuals are dysregulation of cytokine production and CD4 down-regulation in both T-helper cells and monocytes/macrophages. The HIV-1 envelope glycoprotein 120 (gp120) has the ability to induce different cytokines in peripheral blood mononuclear cells and in monocytes/macrophages in vitro which in some instances have been reported to down-regulate macrophage CD4 expression. This study provides evidence that HIV-1 recombinant gp120 (rgp120) down-regulates both surface and total CD4 expression in Primary Tissue Culture-differentiated macrophages (TCDM) at the level of transcription. The CD4 down-regulation observed in TCDM occurred between 6 and 12 hr after rgp120 treatment preceded by a peak of endogenous tumour necrosis factor-alpha (TNF-alpha) observed at 3-6 hr post-treatment. We demonstrate that the TCDM CD4 down-regulation observed after rgp120 treatment was inhibited by the use of an anti-huTNF-alpha monoclonal antibody (mAb), but not by mAb directed against other cytokines induced by rgp120, such as interleukin-1 beta (IL-1 beta) and interferon-alpha (IFN-alpha). The present findings roughly parallel those observed both in the sera of patients and in the monocytes/macrophages isolated from HIV-positive individuals, suggesting that gp120 by stimulating endogenous TNF-alpha production could be a good candidate for the CD4 down-regulation observed in the monocytes/macrophages of HIV-1-infected individuals. In contrast to CD4 down-regulation in HIV-infected lymphocytes, which results from a direct effect of viral genes on CD4 expression, soluble factors such as cytokines induced during HIV infection might explain the monocyte/macrophage CD4 dysregulation observed in acquired immune deficiency syndrome.

Siamon Gordon - One of the best experts on this subject based on the ideXlab platform.

  • hiv 1 induces tumour necrosis factor and il 1 gene expression in Primary human macrophages independent of productive infection
    Clinical and Experimental Immunology, 2008
    Co-Authors: G Herbein, Satish Keshav, Matthew Collin, Luis J Montaner, Siamon Gordon
    Abstract:

    Cytokines such as tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta may play a role in immunopathogenesis of AIDS. We studied early effects (0.5-48 h) of monocytotropic (ADA) or lymphotropic (IIIB) strains of HIV-1 on TNF-alpha and IL-1 beta mRNA expression in Primary human macrophages by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Three-day-old monocyte-derived macrophages were exposed either to Tissue Culture supernatants containing virus (at multiplicity of infection (m.o.i.) of 0.05) or to control supernatants free of virions and gp120. ADA strain, but not IIIB, replicated in Primary Tissue Culture-differentiated macrophages (TCDM). Soluble CD4 (sCD4) was used to inhibit binding of both strains to macrophages. We found that TNF-alpha and IL-1 beta gene expression was induced by both strains 0.5-3 h after addition of virus, and that enhanced expression of both cytokines was inhibited by sCD4. We conclude that CD4-dependent binding to the cell surface is sufficient to enhance TNF-alpha and IL-1 beta mRNA, whereas productive viral replication in Primary human macrophages is not required. Therefore, similar pathways regulate gene expression of TNF-alpha and IL-1 beta by macrophages during initial infection by HIV-1 in vitro.

  • hiv 1 envelope glycoprotein gp120 down regulates cd4 expression in Primary human macrophages through induction of endogenous tumour necrosis factor alpha
    Immunology, 1996
    Co-Authors: V Karsten, Siamon Gordon, A Kirn, G Herbein
    Abstract:

    Among immunological abnormalities present in human immunodeficiency virus type 1 (HIV-1)-infected individuals are dysregulation of cytokine production and CD4 down-regulation in both T-helper cells and monocytes/macrophages. The HIV-1 envelope glycoprotein 120 (gp120) has the ability to induce different cytokines in peripheral blood mononuclear cells and in monocytes/macrophages in vitro which in some instances have been reported to down-regulate macrophage CD4 expression. This study provides evidence that HIV-1 recombinant gp120 (rgp120) down-regulates both surface and total CD4 expression in Primary Tissue Culture-differentiated macrophages (TCDM) at the level of transcription. The CD4 down-regulation observed in TCDM occurred between 6 and 12 hr after rgp120 treatment preceded by a peak of endogenous tumour necrosis factor-alpha (TNF-alpha) observed at 3-6 hr post-treatment. We demonstrate that the TCDM CD4 down-regulation observed after rgp120 treatment was inhibited by the use of an anti-huTNF-alpha monoclonal antibody (mAb), but not by mAb directed against other cytokines induced by rgp120, such as interleukin-1 beta (IL-1 beta) and interferon-alpha (IFN-alpha). The present findings roughly parallel those observed both in the sera of patients and in the monocytes/macrophages isolated from HIV-positive individuals, suggesting that gp120 by stimulating endogenous TNF-alpha production could be a good candidate for the CD4 down-regulation observed in the monocytes/macrophages of HIV-1-infected individuals. In contrast to CD4 down-regulation in HIV-infected lymphocytes, which results from a direct effect of viral genes on CD4 expression, soluble factors such as cytokines induced during HIV infection might explain the monocyte/macrophage CD4 dysregulation observed in acquired immune deficiency syndrome.

Christina Woodbouwens - One of the best experts on this subject based on the ideXlab platform.

  • single cell transcriptome analysis identifies distinct cell types and niche signaling in a Primary gastric organoid model
    Scientific Reports, 2019
    Co-Authors: Jiamin Chen, Billy T Lau, Noemi Andor, Susan M Grimes, Christine Handy, Christina Woodbouwens
    Abstract:

    The diverse cellular milieu of the gastric Tissue microenvironment plays a critical role in normal Tissue homeostasis and tumor development. However, few cell Culture model can recapitulate the Tissue microenvironment and intercellular signaling in vitro. We used a Primary Tissue Culture system to generate a murine p53 null gastric Tissue model containing both epithelium and mesenchymal stroma. To characterize the microenvironment and niche signaling, we used single cell RNA sequencing (scRNA-Seq) to determine the transcriptomes of 4,391 individual cells. Based on specific markers, we identified epithelial cells, fibroblasts and macrophages in initial Tissue explants during organoid formation. The majority of macrophages were polarized towards wound healing and tumor promotion M2-type. During the course of time, the organoids maintained both epithelial and fibroblast lineages with the features of immature mouse gastric stomach. We detected a subset of cells in both lineages expressing Lgr5, one of the stem cell markers. We examined the lineage-specific Wnt signaling activation, and identified that Rspo3 was specifically expressed in the fibroblast lineage, providing an endogenous source of the R-spondin to activate Wnt signaling. Our studies demonstrate that this Primary Tissue Culture system enables one to study gastric Tissue niche signaling and immune response in vitro.

  • single cell transcriptome analysis identifies distinct cell types and intercellular niche signaling in a Primary gastric organoid model
    bioRxiv, 2017
    Co-Authors: Jiamin Chen, Billy T Lau, Noemi Andor, Susan M Grimes, Christine Handy, Christina Woodbouwens
    Abstract:

    The stomach is composed of multiple cell types that include epithelial and surrounding stromal components. The diverse cellular milieu of the gastric Tissue microenvironment plays a critical role in normal Tissue homeostasis as well as tumor development. However, little is know about the mediators of intercellular communication among these different cell types in the stomach. To recapitulate features of the gastric cellular microenvironment and intercellular signaling in vitro, we applied a system to maintain Primary gastric Tissue in an air-liquid interface. Referred to as organoids, this method of Primary Tissue Culture replicates the critical microenvironment of different cellular lineages such as epithelium and endogenous mesenchymal stroma. We analyzed the transcriptomes of over 5,000 individual cells from this Primary gastric Tissue Culture. Based on gene expression of cell type specific markers, we identified epithelial cells, fibroblasts and macrophages that makeup the gastric Tissue at the early stage of organoid formation. Importantly, we found that macrophages in the Tissue explant microenvironment were polarized towards wound healing and tumor promotion. During the course of time, the gastric organoids maintained both epithelial and fibroblast lineages. We detected a subset of cells in both lineages expressing stem cell marker Lgr5, the lineage-specific Wnt signaling activation, and identified that Rspo3, a Wnt agonist, was specifically expressed in the mesenchymal fibroblast lineage. Wnt4 was significantly enriched in the epithelial cells. Thus, these genomic results implicated potential growth factors involved in cell lineage crosstalk in the local microenvironment. These results suggested that the fibroblast cells in stroma provide an endogenous source of the R-spondin to activate Wnt signaling in tumor cells. Our results implicate RSPO3 as a part of the tumor-promoting microenvironment and a potential therapeutic target.

Jiamin Chen - One of the best experts on this subject based on the ideXlab platform.

  • single cell transcriptome analysis identifies distinct cell types and niche signaling in a Primary gastric organoid model
    Scientific Reports, 2019
    Co-Authors: Jiamin Chen, Billy T Lau, Noemi Andor, Susan M Grimes, Christine Handy, Christina Woodbouwens
    Abstract:

    The diverse cellular milieu of the gastric Tissue microenvironment plays a critical role in normal Tissue homeostasis and tumor development. However, few cell Culture model can recapitulate the Tissue microenvironment and intercellular signaling in vitro. We used a Primary Tissue Culture system to generate a murine p53 null gastric Tissue model containing both epithelium and mesenchymal stroma. To characterize the microenvironment and niche signaling, we used single cell RNA sequencing (scRNA-Seq) to determine the transcriptomes of 4,391 individual cells. Based on specific markers, we identified epithelial cells, fibroblasts and macrophages in initial Tissue explants during organoid formation. The majority of macrophages were polarized towards wound healing and tumor promotion M2-type. During the course of time, the organoids maintained both epithelial and fibroblast lineages with the features of immature mouse gastric stomach. We detected a subset of cells in both lineages expressing Lgr5, one of the stem cell markers. We examined the lineage-specific Wnt signaling activation, and identified that Rspo3 was specifically expressed in the fibroblast lineage, providing an endogenous source of the R-spondin to activate Wnt signaling. Our studies demonstrate that this Primary Tissue Culture system enables one to study gastric Tissue niche signaling and immune response in vitro.

  • single cell transcriptome analysis identifies distinct cell types and intercellular niche signaling in a Primary gastric organoid model
    bioRxiv, 2017
    Co-Authors: Jiamin Chen, Billy T Lau, Noemi Andor, Susan M Grimes, Christine Handy, Christina Woodbouwens
    Abstract:

    The stomach is composed of multiple cell types that include epithelial and surrounding stromal components. The diverse cellular milieu of the gastric Tissue microenvironment plays a critical role in normal Tissue homeostasis as well as tumor development. However, little is know about the mediators of intercellular communication among these different cell types in the stomach. To recapitulate features of the gastric cellular microenvironment and intercellular signaling in vitro, we applied a system to maintain Primary gastric Tissue in an air-liquid interface. Referred to as organoids, this method of Primary Tissue Culture replicates the critical microenvironment of different cellular lineages such as epithelium and endogenous mesenchymal stroma. We analyzed the transcriptomes of over 5,000 individual cells from this Primary gastric Tissue Culture. Based on gene expression of cell type specific markers, we identified epithelial cells, fibroblasts and macrophages that makeup the gastric Tissue at the early stage of organoid formation. Importantly, we found that macrophages in the Tissue explant microenvironment were polarized towards wound healing and tumor promotion. During the course of time, the gastric organoids maintained both epithelial and fibroblast lineages. We detected a subset of cells in both lineages expressing stem cell marker Lgr5, the lineage-specific Wnt signaling activation, and identified that Rspo3, a Wnt agonist, was specifically expressed in the mesenchymal fibroblast lineage. Wnt4 was significantly enriched in the epithelial cells. Thus, these genomic results implicated potential growth factors involved in cell lineage crosstalk in the local microenvironment. These results suggested that the fibroblast cells in stroma provide an endogenous source of the R-spondin to activate Wnt signaling in tumor cells. Our results implicate RSPO3 as a part of the tumor-promoting microenvironment and a potential therapeutic target.

Christine Handy - One of the best experts on this subject based on the ideXlab platform.

  • single cell transcriptome analysis identifies distinct cell types and niche signaling in a Primary gastric organoid model
    Scientific Reports, 2019
    Co-Authors: Jiamin Chen, Billy T Lau, Noemi Andor, Susan M Grimes, Christine Handy, Christina Woodbouwens
    Abstract:

    The diverse cellular milieu of the gastric Tissue microenvironment plays a critical role in normal Tissue homeostasis and tumor development. However, few cell Culture model can recapitulate the Tissue microenvironment and intercellular signaling in vitro. We used a Primary Tissue Culture system to generate a murine p53 null gastric Tissue model containing both epithelium and mesenchymal stroma. To characterize the microenvironment and niche signaling, we used single cell RNA sequencing (scRNA-Seq) to determine the transcriptomes of 4,391 individual cells. Based on specific markers, we identified epithelial cells, fibroblasts and macrophages in initial Tissue explants during organoid formation. The majority of macrophages were polarized towards wound healing and tumor promotion M2-type. During the course of time, the organoids maintained both epithelial and fibroblast lineages with the features of immature mouse gastric stomach. We detected a subset of cells in both lineages expressing Lgr5, one of the stem cell markers. We examined the lineage-specific Wnt signaling activation, and identified that Rspo3 was specifically expressed in the fibroblast lineage, providing an endogenous source of the R-spondin to activate Wnt signaling. Our studies demonstrate that this Primary Tissue Culture system enables one to study gastric Tissue niche signaling and immune response in vitro.

  • single cell transcriptome analysis identifies distinct cell types and intercellular niche signaling in a Primary gastric organoid model
    bioRxiv, 2017
    Co-Authors: Jiamin Chen, Billy T Lau, Noemi Andor, Susan M Grimes, Christine Handy, Christina Woodbouwens
    Abstract:

    The stomach is composed of multiple cell types that include epithelial and surrounding stromal components. The diverse cellular milieu of the gastric Tissue microenvironment plays a critical role in normal Tissue homeostasis as well as tumor development. However, little is know about the mediators of intercellular communication among these different cell types in the stomach. To recapitulate features of the gastric cellular microenvironment and intercellular signaling in vitro, we applied a system to maintain Primary gastric Tissue in an air-liquid interface. Referred to as organoids, this method of Primary Tissue Culture replicates the critical microenvironment of different cellular lineages such as epithelium and endogenous mesenchymal stroma. We analyzed the transcriptomes of over 5,000 individual cells from this Primary gastric Tissue Culture. Based on gene expression of cell type specific markers, we identified epithelial cells, fibroblasts and macrophages that makeup the gastric Tissue at the early stage of organoid formation. Importantly, we found that macrophages in the Tissue explant microenvironment were polarized towards wound healing and tumor promotion. During the course of time, the gastric organoids maintained both epithelial and fibroblast lineages. We detected a subset of cells in both lineages expressing stem cell marker Lgr5, the lineage-specific Wnt signaling activation, and identified that Rspo3, a Wnt agonist, was specifically expressed in the mesenchymal fibroblast lineage. Wnt4 was significantly enriched in the epithelial cells. Thus, these genomic results implicated potential growth factors involved in cell lineage crosstalk in the local microenvironment. These results suggested that the fibroblast cells in stroma provide an endogenous source of the R-spondin to activate Wnt signaling in tumor cells. Our results implicate RSPO3 as a part of the tumor-promoting microenvironment and a potential therapeutic target.