The Experts below are selected from a list of 117 Experts worldwide ranked by ideXlab platform

Massimo M. Santoro - One of the best experts on this subject based on the ideXlab platform.

  • Loss of pyruvate kinase M2 limits growth and triggers innate immune signaling in endothelial cells
    Nature Communications, 2018
    Co-Authors: Oliver A. Stone, Mohamed A. El-brolosy, Kerstin Wilhelm, Ana M. Romão, Elisabetta Grillo, Stefan Günther, Sylvia Jeratsch, Carsten Kuenne, Thomas Braun, Massimo M. Santoro
    Abstract:

    Despite their inherent proximity to circulating oxygen and nutrients, endothelial cells (ECs) oxidize only a minor fraction of glucose in mitochondria, a metabolic specialization that is poorly understood. Here we show that the glycolytic enzyme pyruvate kinase M2 (PKM2) limits glucose oxidation, and maintains the growth and epigenetic state of ECs. We find that loss of PKM2 alters mitochondrial substrate utilization and impairs EC proliferation and migration in vivo. Mechanistically, we show that the NF-κB Transcription Factor RelB is responsive to PKM2 loss, limiting EC growth through the regulation of P53. Furthermore, S-adenosylmethionine synthesis is impaired in the absence of PKM2, resulting in DNA hypomethylation, de-repression of endogenous retroviral elements (ERVs) and activation of antiviral innate immune signalling. This work reveals the metabolic and functional consequences of glucose oxidation in the endothelium, highlights the importance of PKM2 for endothelial growth and links metabolic dysfunction with autoimmune activation in ECs. The glycolytic enzyme pyruvate kinase M2 (PKM2) is required for nucleotide synthesis and cell proliferation. Using gene expression and metabolomics analyses, the authors here show that PKM2 regulates methionine metabolism and DNA methylation in endothelial cells.

Ken Shortman - One of the best experts on this subject based on the ideXlab platform.

  • RelB Is Essential for the Development of Myeloid-Related CD8α− Dendritic Cells but Not of Lymphoid-Related CD8α+ Dendritic Cells
    Immunity, 1998
    Co-Authors: Li Wu, Angela D'amico, Kenneth D Winkel, David Lo, Mark Suter, Ken Shortman
    Abstract:

    Abstract The Transcription Factor RelB had been shown to be important for dendritic cell (DC) development, but the type of DC involved was not clear. Here, we report that RelB mRNA is expressed strongly in CD8α − DEC-205 − DC but only weakly in CD8α + DEC-205 + DC. In addition, CD8α + DEC-205 + DC are present and functional in RelB null mice, the DC deficiency being mainly in the CD8α − DEC-205 − population. By constructing bone-marrow chimeric mice, we demonstrate that the partial deficiency in RelB null thymic DC is a secondary effect of disrupted thymic architecture. However, the deficiency in splenic CD8α − DEC-205 − DC is a direct, stem cell intrinsic effect of the RelB mutation. Thus, RelB selectively regulates a myeloid-related DC lineage.

  • RelB is essential for the development of myeloid-related CD8alpha- dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells.
    Immunity, 1998
    Co-Authors: Lingfeng Wu, Marcel Suter, Angela D'amico, D Lo, Kenneth D Winkel, Ken Shortman
    Abstract:

    The Transcription Factor RelB had been shown to be important for dendritic cell (DC) development, but the type of DC involved was not clear. Here, we report that RelB mRNA is expressed strongly in CD8alpha- DEC-205- DC but only weakly in CD8alpha+ DEC-205+ DC. In addition, CD8alpha+ DEC-205+ DC are present and functional in RelB null mice, the DC deficiency being mainly in the CD8alpha- DEC-205- population. By constructing bone-marrow chimeric mice, we demonstrate that the partial deficiency in RelB null thymic DC is a secondary effect of disrupted thymic architecture. However, the deficiency in splenic CD8alpha- DEC-205- DC is a direct, stem cell intrinsic effect of the RelB mutation. Thus, RelB selectively regulates a myeloid-related DC lineage.

Qiu Yurong - One of the best experts on this subject based on the ideXlab platform.

  • The effect of nuclear Factor RelB suppression on the induction of immunological tolerance in vitro of mice bone marrow-derived dendritic cells
    Current Immunology, 2020
    Co-Authors: Qiu Yurong
    Abstract:

    Mouse bone marrow derived dendritic cells(DC) were cultured in RPMI 1640 with recombinant mouse granulocyte-macrophage colony-stimulating Factor(rmGM-CSF) and interleukin-4(rmIL-4),and purified by CD11c+ microbead.RelB sh-RNA lentivirus were prepared by using kits of Invitrogen Corp,and co-cultured with mouse bone marrow derived dendritic cells,then surface molecules(MHCⅡ,CD86 and CD40) expression level were determined by flow cytometry(FCM),and the mouse T cells were purified by CD3+ microbeads.Then T cell proliferation capacity and Th cytokine detected by MTT approach,and by liquid chip approach respectively.Mature DC(that is,LPS-DC) worked as control group,at the same time,we also designed an immature DC and LPS RNAi RelB DC.We found that the expression levels of co-stimulatory molecules(CD86 and CD40) and MHCⅡ class molecule were low in DCs of nuclear Factor RelB suppression,but significantly high comparing with mature DCs(P0.01),and LPS RNAi RelB DC(that is,after RNAi RelB DC stimulated by LPS) surface of three class molecules also had a low level compared with LPS DC(P0.01).To some extent,the expression levels of surface molecules in RNAi RelB DC were near to them of immature DC.T cells proliferation capacities and Th cytokines in DCs of nuclear Transcription Factor RelB suppression were significantly lower than those in mature DCs(P0.05),having the same low levels with the immature DCs.It showed us that DCs of nuclear Factor RelB suppression have the capacities which induce immunological tolerance in vitro.This is a novel pathway to research tolerogenic dendritic cells.

  • the effect of nuclear Transcription Factor RelB suppression on the surface molecules of dendritic cells
    Journal of Tropical Medicine, 2010
    Co-Authors: Wang Qian, Xiong Shilong, Jiang Chaoxin, Qiu Yurong
    Abstract:

    Objective To explore the effect of nuclear Transcription Factor RelB suppression on the expression of surface molecules of bone marrow derived dendritic cells and provide a novel pathway for researching tolerogenic dendritic cells. Methods Mouse bone marrow derived dendritic cells were cultured with recombinant mouse granulocyte-macrophage colony-stimulating Factor (rmGM-CSF) and interleukin-4 (IL-4),and then purified by CD11c+ microbead. RelB shRNA lentivirus were prepared by using kits of Invitrogen Corp,and co-cultured with mouse bone marrow dendritic cells. The surface molecules (MHC-II,CD86 and CD40) expression levels were detected by flow cytometry (FCM). Mature DC (that is,LPS-DC) worked as control group,at the same time,immature DC and LPS RNAi RelB DC were used for comparison. Results The expression levels of co-stimulatory molecules (CD86 and CD40) and MHC-II class molecule were low in DCs of nuclear Transcription Factor RelB suppression,but significantly high in mature DC (P0.05). In LPS RNAi RelB DC(that is,after RNAi RelB DC stimulated by LPS) surface the expression levels of CD86,CD40 and MHC-II molecules were low compared with LPS DC(P0.05). To some extent,the expression levels of surface molecules in RNAi RelB DC were similar to that of immature DC. Conclusion The expression levels of surface molecules were low in DCs with nuclear Transcription Factor RelB suppression. DCs have the same characteristics with tolerogenic dendritic cells. This is a novel direction to research tolerogenic dendritic cells.

Oliver A. Stone - One of the best experts on this subject based on the ideXlab platform.

  • Loss of pyruvate kinase M2 limits growth and triggers innate immune signaling in endothelial cells
    Nature Communications, 2018
    Co-Authors: Oliver A. Stone, Mohamed A. El-brolosy, Kerstin Wilhelm, Ana M. Romão, Elisabetta Grillo, Stefan Günther, Sylvia Jeratsch, Carsten Kuenne
    Abstract:

    Despite their inherent proximity to circulating oxygen and nutrients, endothelial cells (ECs) oxidize only a minor fraction of glucose in mitochondria, a metabolic specialization that is poorly understood. Here we show that the glycolytic enzyme pyruvate kinase M2 (PKM2) limits glucose oxidation, and maintains the growth and epigenetic state of ECs. We find that loss of PKM2 alters mitochondrial substrate utilization and impairs EC proliferation and migration in vivo. Mechanistically, we show that the NF-κB Transcription Factor RelB is responsive to PKM2 loss, limiting EC growth through the regulation of P53. Furthermore, S-adenosylmethionine synthesis is impaired in the absence of PKM2, resulting in DNA hypomethylation, de-repression of endogenous retroviral elements (ERVs) and activation of antiviral innate immune signalling. This work reveals the metabolic and functional consequences of glucose oxidation in the endothelium, highlights the importance of PKM2 for endothelial growth and links metabolic dysfunction with autoimmune activation in ECs.

  • Loss of pyruvate kinase M2 limits growth and triggers innate immune signaling in endothelial cells
    Nature Communications, 2018
    Co-Authors: Oliver A. Stone, Mohamed A. El-brolosy, Kerstin Wilhelm, Ana M. Romão, Elisabetta Grillo, Stefan Günther, Sylvia Jeratsch, Carsten Kuenne, Thomas Braun, Massimo M. Santoro
    Abstract:

    Despite their inherent proximity to circulating oxygen and nutrients, endothelial cells (ECs) oxidize only a minor fraction of glucose in mitochondria, a metabolic specialization that is poorly understood. Here we show that the glycolytic enzyme pyruvate kinase M2 (PKM2) limits glucose oxidation, and maintains the growth and epigenetic state of ECs. We find that loss of PKM2 alters mitochondrial substrate utilization and impairs EC proliferation and migration in vivo. Mechanistically, we show that the NF-κB Transcription Factor RelB is responsive to PKM2 loss, limiting EC growth through the regulation of P53. Furthermore, S-adenosylmethionine synthesis is impaired in the absence of PKM2, resulting in DNA hypomethylation, de-repression of endogenous retroviral elements (ERVs) and activation of antiviral innate immune signalling. This work reveals the metabolic and functional consequences of glucose oxidation in the endothelium, highlights the importance of PKM2 for endothelial growth and links metabolic dysfunction with autoimmune activation in ECs. The glycolytic enzyme pyruvate kinase M2 (PKM2) is required for nucleotide synthesis and cell proliferation. Using gene expression and metabolomics analyses, the authors here show that PKM2 regulates methionine metabolism and DNA methylation in endothelial cells.

Carsten Kuenne - One of the best experts on this subject based on the ideXlab platform.

  • Loss of pyruvate kinase M2 limits growth and triggers innate immune signaling in endothelial cells
    Nature Communications, 2018
    Co-Authors: Oliver A. Stone, Mohamed A. El-brolosy, Kerstin Wilhelm, Ana M. Romão, Elisabetta Grillo, Stefan Günther, Sylvia Jeratsch, Carsten Kuenne
    Abstract:

    Despite their inherent proximity to circulating oxygen and nutrients, endothelial cells (ECs) oxidize only a minor fraction of glucose in mitochondria, a metabolic specialization that is poorly understood. Here we show that the glycolytic enzyme pyruvate kinase M2 (PKM2) limits glucose oxidation, and maintains the growth and epigenetic state of ECs. We find that loss of PKM2 alters mitochondrial substrate utilization and impairs EC proliferation and migration in vivo. Mechanistically, we show that the NF-κB Transcription Factor RelB is responsive to PKM2 loss, limiting EC growth through the regulation of P53. Furthermore, S-adenosylmethionine synthesis is impaired in the absence of PKM2, resulting in DNA hypomethylation, de-repression of endogenous retroviral elements (ERVs) and activation of antiviral innate immune signalling. This work reveals the metabolic and functional consequences of glucose oxidation in the endothelium, highlights the importance of PKM2 for endothelial growth and links metabolic dysfunction with autoimmune activation in ECs.

  • Loss of pyruvate kinase M2 limits growth and triggers innate immune signaling in endothelial cells
    Nature Communications, 2018
    Co-Authors: Oliver A. Stone, Mohamed A. El-brolosy, Kerstin Wilhelm, Ana M. Romão, Elisabetta Grillo, Stefan Günther, Sylvia Jeratsch, Carsten Kuenne, Thomas Braun, Massimo M. Santoro
    Abstract:

    Despite their inherent proximity to circulating oxygen and nutrients, endothelial cells (ECs) oxidize only a minor fraction of glucose in mitochondria, a metabolic specialization that is poorly understood. Here we show that the glycolytic enzyme pyruvate kinase M2 (PKM2) limits glucose oxidation, and maintains the growth and epigenetic state of ECs. We find that loss of PKM2 alters mitochondrial substrate utilization and impairs EC proliferation and migration in vivo. Mechanistically, we show that the NF-κB Transcription Factor RelB is responsive to PKM2 loss, limiting EC growth through the regulation of P53. Furthermore, S-adenosylmethionine synthesis is impaired in the absence of PKM2, resulting in DNA hypomethylation, de-repression of endogenous retroviral elements (ERVs) and activation of antiviral innate immune signalling. This work reveals the metabolic and functional consequences of glucose oxidation in the endothelium, highlights the importance of PKM2 for endothelial growth and links metabolic dysfunction with autoimmune activation in ECs. The glycolytic enzyme pyruvate kinase M2 (PKM2) is required for nucleotide synthesis and cell proliferation. Using gene expression and metabolomics analyses, the authors here show that PKM2 regulates methionine metabolism and DNA methylation in endothelial cells.