The Experts below are selected from a list of 80199 Experts worldwide ranked by ideXlab platform
Jeanfrancois Arnal - One of the best experts on this subject based on the ideXlab platform.
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membrane and nuclear estrogen receptor alpha actions from Tissue Specificity to medical implications
Physical Review, 2017Co-Authors: Jeanfrancois Arnal, Francoise Lenfant, Raphael Metivier, Gilles FlouriotAbstract:Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive Tissues. In this review, we attempt to summarize the in vitro studies that are the basis of our current understanding of the mechanisms of action of ERα as a nuclear receptor and the key roles played by its two activation functions (AFs) in its transcriptional activities. We then depict the consequences of the selective inactivation of these AFs in mouse models, focusing on the prominent roles played by ERα in the reproductive tract and in the vascular system. Evidence has accumulated over the two last decades that ERα is also associated with the plasma membrane and activates non-nuclear signaling from this site. These rapid/nongenomic/membrane-initiated steroid signals (MISS) have been characterized in a variety of cell lines, and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS and the generation of mice expressing an ERα protein impeded for membrane localization have begun to unravel the physiological role of MISS in vivo. Finally, we discuss novel perspectives for the design of Tissue-selective ER modulators based on the integration of the physiological and pathophysiological roles of MISS actions of estrogens.
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membrane and nuclear estrogen receptor alpha actions from Tissue Specificity to medical implications
Physiological Reviews, 2017Co-Authors: Jeanfrancois Arnal, Francoise Lenfant, Raphael Metivier, Gilles FlouriotAbstract:Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive Tissues. In this review, we attemp...
Francoise Lenfant - One of the best experts on this subject based on the ideXlab platform.
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membrane and nuclear estrogen receptor alpha actions from Tissue Specificity to medical implications
Physical Review, 2017Co-Authors: Jeanfrancois Arnal, Francoise Lenfant, Raphael Metivier, Gilles FlouriotAbstract:Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive Tissues. In this review, we attempt to summarize the in vitro studies that are the basis of our current understanding of the mechanisms of action of ERα as a nuclear receptor and the key roles played by its two activation functions (AFs) in its transcriptional activities. We then depict the consequences of the selective inactivation of these AFs in mouse models, focusing on the prominent roles played by ERα in the reproductive tract and in the vascular system. Evidence has accumulated over the two last decades that ERα is also associated with the plasma membrane and activates non-nuclear signaling from this site. These rapid/nongenomic/membrane-initiated steroid signals (MISS) have been characterized in a variety of cell lines, and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS and the generation of mice expressing an ERα protein impeded for membrane localization have begun to unravel the physiological role of MISS in vivo. Finally, we discuss novel perspectives for the design of Tissue-selective ER modulators based on the integration of the physiological and pathophysiological roles of MISS actions of estrogens.
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membrane and nuclear estrogen receptor alpha actions from Tissue Specificity to medical implications
Physiological Reviews, 2017Co-Authors: Jeanfrancois Arnal, Francoise Lenfant, Raphael Metivier, Gilles FlouriotAbstract:Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive Tissues. In this review, we attemp...
Raphael Metivier - One of the best experts on this subject based on the ideXlab platform.
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membrane and nuclear estrogen receptor alpha actions from Tissue Specificity to medical implications
Physical Review, 2017Co-Authors: Jeanfrancois Arnal, Francoise Lenfant, Raphael Metivier, Gilles FlouriotAbstract:Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive Tissues. In this review, we attempt to summarize the in vitro studies that are the basis of our current understanding of the mechanisms of action of ERα as a nuclear receptor and the key roles played by its two activation functions (AFs) in its transcriptional activities. We then depict the consequences of the selective inactivation of these AFs in mouse models, focusing on the prominent roles played by ERα in the reproductive tract and in the vascular system. Evidence has accumulated over the two last decades that ERα is also associated with the plasma membrane and activates non-nuclear signaling from this site. These rapid/nongenomic/membrane-initiated steroid signals (MISS) have been characterized in a variety of cell lines, and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS and the generation of mice expressing an ERα protein impeded for membrane localization have begun to unravel the physiological role of MISS in vivo. Finally, we discuss novel perspectives for the design of Tissue-selective ER modulators based on the integration of the physiological and pathophysiological roles of MISS actions of estrogens.
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membrane and nuclear estrogen receptor alpha actions from Tissue Specificity to medical implications
Physiological Reviews, 2017Co-Authors: Jeanfrancois Arnal, Francoise Lenfant, Raphael Metivier, Gilles FlouriotAbstract:Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive Tissues. In this review, we attemp...
Gilles Flouriot - One of the best experts on this subject based on the ideXlab platform.
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membrane and nuclear estrogen receptor alpha actions from Tissue Specificity to medical implications
Physical Review, 2017Co-Authors: Jeanfrancois Arnal, Francoise Lenfant, Raphael Metivier, Gilles FlouriotAbstract:Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive Tissues. In this review, we attempt to summarize the in vitro studies that are the basis of our current understanding of the mechanisms of action of ERα as a nuclear receptor and the key roles played by its two activation functions (AFs) in its transcriptional activities. We then depict the consequences of the selective inactivation of these AFs in mouse models, focusing on the prominent roles played by ERα in the reproductive tract and in the vascular system. Evidence has accumulated over the two last decades that ERα is also associated with the plasma membrane and activates non-nuclear signaling from this site. These rapid/nongenomic/membrane-initiated steroid signals (MISS) have been characterized in a variety of cell lines, and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS and the generation of mice expressing an ERα protein impeded for membrane localization have begun to unravel the physiological role of MISS in vivo. Finally, we discuss novel perspectives for the design of Tissue-selective ER modulators based on the integration of the physiological and pathophysiological roles of MISS actions of estrogens.
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membrane and nuclear estrogen receptor alpha actions from Tissue Specificity to medical implications
Physiological Reviews, 2017Co-Authors: Jeanfrancois Arnal, Francoise Lenfant, Raphael Metivier, Gilles FlouriotAbstract:Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive Tissues. In this review, we attemp...
Mohamed H Sayegh - One of the best experts on this subject based on the ideXlab platform.
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differential role of ccr2 in islet and heart allograft rejection Tissue Specificity of chemokine chemokine receptor function in vivo
Journal of Immunology, 2004Co-Authors: Reza Abdi, Terry K Means, Toshiro Ito, R N Smith, Nader Najafian, Mollie Jurewicz, Vaja Tchipachvili, Israel F Charo, Hugh Auchincloss, Mohamed H SayeghAbstract:Chemokines have a pivotal role in the mobilization and activation of specific leukocyte subsets in acute allograft rejection. However, the role of specific chemokines and chemokine receptors in islet allograft rejection has not been fully elucidated. We now show that islet allograft rejection is associated with a steady increase in intragraft expression of the chemokines CCL8 (monocyte chemoattractant protein-2), CCL9 (monocyte chemoattractant protein-5), CCL5 (RANTES), CXCL-10 (IFN-γ-inducible protein-10), and CXCL9 (monokine induced by IFN-γ) and their corresponding chemokine receptors CCR2, CCR5, CCR1, and CXCR3. Because CCR2 was found to be highly induced, we tested the specific role of CCR2 in islet allograft rejection by transplanting fully MHC mismatched islets from BALB/c mice into C57BL/6 wild-type (WT) and CCR2-deficient mice (CCR2 −/− ). A significant prolongation of islet allograft survival was noted in CCR2 −/− recipients, with median survival time of 24 and 12 days for CCR2 −/− and WT recipients, respectively ( p + , but not CD4 + effector alloreactive T cells (CD62L low CD44 high ) in CCR2 −/− compared with WT recipients. In addition, CCR2 −/− recipients had a reduced Th1 and increased Th2 alloresponse in the periphery (by ELISPOT analysis) as well as in the grafts (by RT-PCR). However, these changes were only transient in CCR2 −/− recipients that ultimately rejected their grafts. Furthermore, in contrast to the islet transplants, CCR2 deficiency offered only marginal prolongation of heart allograft survival. This study demonstrates the important role for CCR2 in early islet allograft rejection and highlights the Tissue Specificity of the chemokine/chemokine receptor system in vivo in regulating allograft rejection.
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differential role of ccr2 in islet and heart allograft rejection Tissue Specificity of chemokine chemokine receptor function in vivo
Journal of Immunology, 2004Co-Authors: Reza Abdi, Terry K Means, Toshiro Ito, R N Smith, Nader Najafian, Mollie Jurewicz, Vaja Tchipachvili, Israel F Charo, Hugh Auchincloss, Mohamed H SayeghAbstract:Chemokines have a pivotal role in the mobilization and activation of specific leukocyte subsets in acute allograft rejection. However, the role of specific chemokines and chemokine receptors in islet allograft rejection has not been fully elucidated. We now show that islet allograft rejection is associated with a steady increase in intragraft expression of the chemokines CCL8 (monocyte chemoattractant protein-2), CCL9 (monocyte chemoattractant protein-5), CCL5 (RANTES), CXCL-10 (IFN-gamma-inducible protein-10), and CXCL9 (monokine induced by IFN-gamma) and their corresponding chemokine receptors CCR2, CCR5, CCR1, and CXCR3. Because CCR2 was found to be highly induced, we tested the specific role of CCR2 in islet allograft rejection by transplanting fully MHC mismatched islets from BALB/c mice into C57BL/6 wild-type (WT) and CCR2-deficient mice (CCR2-/-). A significant prolongation of islet allograft survival was noted in CCR2-/- recipients, with median survival time of 24 and 12 days for CCR2-/- and WT recipients, respectively (p < 0.0001). This was associated with reduction in the generation of CD8+, but not CD4+ effector alloreactive T cells (CD62L(low)CD44(high)) in CCR2-/- compared with WT recipients. In addition, CCR2-/- recipients had a reduced Th1 and increased Th2 alloresponse in the periphery (by ELISPOT analysis) as well as in the grafts (by RT-PCR). However, these changes were only transient in CCR2-/- recipients that ultimately rejected their grafts. Furthermore, in contrast to the islet transplants, CCR2 deficiency offered only marginal prolongation of heart allograft survival. This study demonstrates the important role for CCR2 in early islet allograft rejection and highlights the Tissue Specificity of the chemokine/chemokine receptor system in vivo in regulating allograft rejection.
