The Experts below are selected from a list of 8898 Experts worldwide ranked by ideXlab platform
Monique Dubois-dalcq - One of the best experts on this subject based on the ideXlab platform.
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Differential signalling of the Chemokine receptor CXCR4 by stromal cell-derived factor 1 and the HIV glycoprotein in rat neurons and astrocytes.
European Journal of Neuroscience, 2008Co-Authors: Françoise Lazarini, To Nam Tham, Philippe Casanova, Erik De Clercq, Fernando Arenzana-seisdedos, Françoise Baleux, Monique Dubois-dalcqAbstract:: CXCR4 is the Gi protein-linked seven-transmembrane receptor for the Alpha Chemokine stromal cell-derived factor 1 (SDF-1), a chemoattractant for lymphocytes. This receptor is highly conserved between human and rodent. CXCR4 is also a coreceptor for entry of human immunodeficiency virus (HIV) in T cells and is expressed in the CNS. To investigate how these CXCR4 ligands influence CNS development and/or function, we have examined the expression and signalling of this Chemokine receptor in rat neurons and astrocytes in vitro. CXCR4 transcripts and protein are synthesized by both cell types and in E15 brain neuronal progenitors. In these progenitors, SDF-1, but not gp120 (the HIV glycoprotein), induced activation of extracellular signal regulated kinases (ERKs) 1/2 and a dose-dependent chemotactic response. This chemotaxis was inhibited by Pertussis toxin, which uncouples Gi proteins and the bicyclam AMD3100, a highly selective CXCR4 antagonist, as well as by an inhibitor of the MAP kinase pathway. In differentiated neurons, both SDF-1 and the glycoprotein of HIV, gp120, triggered activation of ERKs with similar kinetics. These effects were significantly inhibited by Pertussis toxin and the CXCR4 antagonist. Rat astrocytes also responded to SDF-1 signalling by phosphorylation of ERKs but, in contrast to cortical neurons, no kinase activation was induced by gp120. Thus neurons and astrocytes can respond differently to signalling by SDF-1 and/or gp120. As SDF-1 triggers directed migration of neuronal progenitors, this Alpha Chemokine may play a role in cortex development. In differentiated neurons, both natural and viral ligands of CXCR4 activate ERKs and may therefore influence neuronal function.
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Developmental pattern of expression of the Alpha Chemokine stromal cell‐derived factor 1 in the rat central nervous system
European Journal of Neuroscience, 2001Co-Authors: To Nam Tham, Françoise Lazarini, Isabelle Franceschini, François Lachapelle, Ali Amara, Monique Dubois-dalcqAbstract:: Stromal cell-derived factor 1 (SDF-1) is an Alpha-Chemokine that stimulates migration of haematopoietic progenitor cells and development of the immune system. SDF-1 is also abundantly and selectively expressed in the developing and mature CNS, as we show here. At embryonic day 15, SDF-1 transcripts were detected in the germinal periventricular zone and in the deep layer of the forming cerebral cortex. At birth, granule cells in the cerebellum and glial cells of the olfactory bulb outer layer showed an SDF-1 in situ hybridization signal that decreased progressively within the next 2 weeks. In other regions such as cortex, thalamus and hippocampus, SDF-1 transcripts detected at birth progressively increased in abundance during the postnatal period. SDF-1 protein was identified by immunoblot and/or immunocytochemistry in most brain regions where these transcripts were detected. SDF-1 was selectively localized in some thalamic nuclei and neurons of the fifth cortical layer as well as in pontine and brainstem nuclei which relay the nociceptive response. The presence of SDF-1 transcripts in cerebellar granule cells was correlated with their migration from the external to the inner granular layers with disappearance of the signal when migration was completed. In contrast, SDF1 mRNA signal increased during formation of the hippocampal dentate gyrus and stayed high in this region throughout life. The selective and regulated expression of SDF-1 in these regions suggests a role in precursor migration, neurogenesis and, possibly, synaptogenesis. Thus this Alpha Chemokine may be as essential to nervous system function as it is to the immune system.
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Differential signalling of the Chemokine receptor CXCR4 by stromal cell-derived factor 1 and the HIV glycoprotein in rat neurons and astrocytes.
The European journal of neuroscience, 2000Co-Authors: Françoise Lazarini, To Nam Tham, Philippe Casanova, Erik De Clercq, Fernando Arenzana-seisdedos, Françoise Baleux, Monique Dubois-dalcqAbstract:CXCR4 is the Gi protein-linked seven-transmembrane receptor for the Alpha Chemokine stromal cell-derived factor 1 (SDF-1), a chemoattractant for lymphocytes. This receptor is highly conserved between human and rodent. CXCR4 is also a coreceptor for entry of human immunodeficiency virus (HIV) in T cells and is expressed in the CNS. To investigate how these CXCR4 ligands influence CNS development and/or function, we have examined the expression and signalling of this Chemokine receptor in rat neurons and astrocytes in vitro. CXCR4 transcripts and protein are synthesized by both cell types and in E15 brain neuronal progenitors. In these progenitors, SDF-1, but not gp120 (the HIV glycoprotein), induced activation of extracellular signal regulated kinases (ERKs) 1/2 and a dose-dependent chemotactic response. This chemotaxis was inhibited by Pertussis toxin, which uncouples Gi proteins and the bicyclam AMD3100, a highly selective CXCR4 antagonist, as well as by an inhibitor of the MAP kinase pathway. In differentiated neurons, both SDF-1 and the glycoprotein of HIV, gp120, triggered activation of ERKs with similar kinetics. These effects were significantly inhibited by Pertussis toxin and the CXCR4 antagonist. Rat astrocytes also responded to SDF-1 signalling by phosphorylation of ERKs but, in contrast to cortical neurons, no kinase activation was induced by gp120. Thus neurons and astrocytes can respond differently to signalling by SDF-1 and/or gp120. As SDF-1 triggers directed migration of neuronal progenitors, this Alpha Chemokine may play a role in cortex development. In differentiated neurons, both natural and viral ligands of CXCR4 activate ERKs and may therefore influence neuronal function.
Mariusz Z Ratajczak - One of the best experts on this subject based on the ideXlab platform.
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Role of C3a in Regulating Thymocyte Infection by HIV-1.
2017Co-Authors: Tomasz Rozmyslowicz, Mariusz Z Ratajczak, Dareus O. Conover, Glen N. GaultonAbstract:The primary physiological role of complement proteins lies in augmenting host defense to microorganisms. Among several cascade products, complement components C3 and C5 are cleaved and activated through proteolytic processing during immune activation following exposure to HIV-1. This reaction generates the small peptide anaphylatoxins C3a and C5a, which bind to G-protein coupled membrane receptors that sensitize the response of human T-lymphocytic cells to multiple cytokines including CXCL12/SDF-1. CXCL12 is an Alpha Chemokine that binds to the CXCR4 membrane receptor, which also functions as a co-receptor for X4-tropic HIV-1. Given the importance of complement activation in immune function and the bioactive nature of complement cleavage products we investigated here the role of C3a in HIV-1 infection of human thymocytes. Our data illustrate a potential new link between HIV-1 infection and complement activation in which C3a anaphylatoxin may modulate infectivity by reducing the susceptibility of thymocytes to HIV-1 infection.
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The role of stromal-derived factor-1--CXCR7 axis in development and cancer.
European journal of pharmacology, 2009Co-Authors: Radoslaw B Maksym, Maciej Tarnowski, Katarzyna Grymula, Joanna Tarnowska, Marcin Wysoczynski, Boguslaw Czerny, Janina Ratajczak, Magda Kucia, Mariusz Z RatajczakAbstract:Cancer metastasis is a major clinical problem that contributes to unsuccessful therapy. Augmenting evidence indicates that metastasizing cancer cells employ several mechanisms that are involved in developmental trafficking of normal stem cells. Stromal-derived factor-1 (SDF-1) is an important Alpha-Chemokine that binds to the G-protein-coupled seven-transmembrane span CXCR4. The SDF-1-CXCR4 axis regulates trafficking of normal and malignant cells. SDF-1 is an important chemoattractant for a variety of cells including hematopoietic stem/progenitor cells. For many years, it was believed that CXCR4 was the only receptor for SDF-1. However, several reports recently provided evidence that SDF-1 also binds to another seven-transmembrane span receptor called CXCR7, sharing this receptor with another Chemokine family member called Interferon-inducible T-cell chemoattractant (I-TAC). Thus, with CXCR7 identified as a new receptor for SDF-1, the role of the SDF-1-CXCR4 axis in regulating several biological processes becomes more complex. Based on the available literature, this review addresses the biological significance of SDF-1's interaction with CXCR7, which may act as a kind of decoy or signaling receptor depending on cell type. Augmenting evidence suggests that CXCR7 is involved in several aspects of tumorogenesis and could become an important target for new anti-metastatic and anti-cancer drugs.
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Biological role of the CXCR4-SDF-1 axis in normal human hematopoietic cells.
Methods in molecular biology (Clifton N.J.), 2006Co-Authors: Marcin Majka, Mariusz Z RatajczakAbstract:Stromal-derived factor (SDF)-1, an Alpha-Chemokine that binds to G protein-coupled seven transmembrane-spanning receptor, CXCR4, plays an important and unique role in regulating the trafficking of normal hematopoietic stem/progenitor cells and their homing/retention in bone marrow. The same axis also modulates several biological processes in more differentiated cells from the granulocyte-monocytic, erythroid, and megakaryocytic lineages. In this chapter, experimental details are described for the isolation of early human hematopoietic cells, such as CD34+ mononuclear cells, myeloblasts, erythroblasts, and megakaryoblasts. These cells can be used routinely for studying the role of the CXCR4-SDF-1 axis in normal human hematopoiesis.
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Circulating CXCR4-positive stem-progenitor cells compete for SDF-1-positive niches in bone marrow, muscle and naural tissues: an alternative hypothesis to stem cell plasticity
Folia Histochemica Et Cytobiologica, 2003Co-Authors: A Pituch-noworolska, Monika Baj-krzyworzeka, Barbara Urbanowicz, Marcin Majka, Edward Malec, Anna Janowska-wieczorek, Mariusz Z RatajczakAbstract:The trans-differentiation hypothesis of adult tissue-specific stem cells has been recently questioned because of insufficient proof that the so-called plasticity experiments were performed on pure populations of tissue-specific stem cells. It was shown recently, for example, that the formation of haematopoietic colonies by muscle cells depended on the presence of haematopoietic stem/progenitor cells residing within the muscle tissue and hence was not related to the plasticity of the muscle stem cells. The explanation for the presence in, or homing into, muscles of haematopoietic stem cells is, however, not clear. In our study, we hypothesised that muscle tissues secrete stromal-derived factor (SDF)- 1, an Alpha-Chemokine for haematopoietic stem cells (HSC), which could attract HSC circulating in peripheral blood into muscle tissue. We found, using RT-PCR and immunocytochemistry, that SDF-1 was expressed in human heart and skeletal muscles. Moreover, muscle satellite cells, which are pivotal for regeneration of muscle, highly expressed on their surface CXCR4, a G-protein-coupled receptor that binds SDF-1. To determine whether the CXCR4 receptor is functional on muscle satellite/progenitor cells, we stimulated murine satellite cells (the C2C12 cell line) with SDF-1 and demonstrated the phosphorylation of p42/44 MAPK and AKT serine-threonine kinase in these cells. Moreover, we showed that SDF-1 gradient chemoattracts these cells. We postulate that the CXCR4-positive muscle satellite and CXCR4-positive HSC circulating in the peripheral blood compete for occupancy of SDF-1-positive stem cell niches that are present in bone marrow and muscle tissues. Thus, we suggest that competition for common niches by various circulating CXCR4-positive stem cells and their ability to home to the SDF-1-positive niches in various organs, is a better explanation than stem cell plasticity of why (i) haematopoietic colonies can be cultured from muscles and (ii) early muscle progenitors could be cultured from bone marrow.
Françoise Lazarini - One of the best experts on this subject based on the ideXlab platform.
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Differential signalling of the Chemokine receptor CXCR4 by stromal cell-derived factor 1 and the HIV glycoprotein in rat neurons and astrocytes.
European Journal of Neuroscience, 2008Co-Authors: Françoise Lazarini, To Nam Tham, Philippe Casanova, Erik De Clercq, Fernando Arenzana-seisdedos, Françoise Baleux, Monique Dubois-dalcqAbstract:: CXCR4 is the Gi protein-linked seven-transmembrane receptor for the Alpha Chemokine stromal cell-derived factor 1 (SDF-1), a chemoattractant for lymphocytes. This receptor is highly conserved between human and rodent. CXCR4 is also a coreceptor for entry of human immunodeficiency virus (HIV) in T cells and is expressed in the CNS. To investigate how these CXCR4 ligands influence CNS development and/or function, we have examined the expression and signalling of this Chemokine receptor in rat neurons and astrocytes in vitro. CXCR4 transcripts and protein are synthesized by both cell types and in E15 brain neuronal progenitors. In these progenitors, SDF-1, but not gp120 (the HIV glycoprotein), induced activation of extracellular signal regulated kinases (ERKs) 1/2 and a dose-dependent chemotactic response. This chemotaxis was inhibited by Pertussis toxin, which uncouples Gi proteins and the bicyclam AMD3100, a highly selective CXCR4 antagonist, as well as by an inhibitor of the MAP kinase pathway. In differentiated neurons, both SDF-1 and the glycoprotein of HIV, gp120, triggered activation of ERKs with similar kinetics. These effects were significantly inhibited by Pertussis toxin and the CXCR4 antagonist. Rat astrocytes also responded to SDF-1 signalling by phosphorylation of ERKs but, in contrast to cortical neurons, no kinase activation was induced by gp120. Thus neurons and astrocytes can respond differently to signalling by SDF-1 and/or gp120. As SDF-1 triggers directed migration of neuronal progenitors, this Alpha Chemokine may play a role in cortex development. In differentiated neurons, both natural and viral ligands of CXCR4 activate ERKs and may therefore influence neuronal function.
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Developmental pattern of expression of the Alpha Chemokine stromal cell‐derived factor 1 in the rat central nervous system
European Journal of Neuroscience, 2001Co-Authors: To Nam Tham, Françoise Lazarini, Isabelle Franceschini, François Lachapelle, Ali Amara, Monique Dubois-dalcqAbstract:: Stromal cell-derived factor 1 (SDF-1) is an Alpha-Chemokine that stimulates migration of haematopoietic progenitor cells and development of the immune system. SDF-1 is also abundantly and selectively expressed in the developing and mature CNS, as we show here. At embryonic day 15, SDF-1 transcripts were detected in the germinal periventricular zone and in the deep layer of the forming cerebral cortex. At birth, granule cells in the cerebellum and glial cells of the olfactory bulb outer layer showed an SDF-1 in situ hybridization signal that decreased progressively within the next 2 weeks. In other regions such as cortex, thalamus and hippocampus, SDF-1 transcripts detected at birth progressively increased in abundance during the postnatal period. SDF-1 protein was identified by immunoblot and/or immunocytochemistry in most brain regions where these transcripts were detected. SDF-1 was selectively localized in some thalamic nuclei and neurons of the fifth cortical layer as well as in pontine and brainstem nuclei which relay the nociceptive response. The presence of SDF-1 transcripts in cerebellar granule cells was correlated with their migration from the external to the inner granular layers with disappearance of the signal when migration was completed. In contrast, SDF1 mRNA signal increased during formation of the hippocampal dentate gyrus and stayed high in this region throughout life. The selective and regulated expression of SDF-1 in these regions suggests a role in precursor migration, neurogenesis and, possibly, synaptogenesis. Thus this Alpha Chemokine may be as essential to nervous system function as it is to the immune system.
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developmental pattern of expression of the Alpha Chemokine stromal cell derived factor 1 in the rat central nervous system
European Journal of Neuroscience, 2001Co-Authors: To Nam Tham, Françoise Lazarini, Isabelle Franceschini, François Lachapelle, Ali Amara, Monique DuboisdalcqAbstract:Stromal cell-derived factor 1 (SDF-1) is an Alpha-Chemokine that stimulates migration of haematopoietic progenitor cells and development of the immune system. SDF-1 is also abundantly and selectively expressed in the developing and mature CNS, as we show here. At embryonic day 15, SDF-1 transcripts were detected in the germinal periventricular zone and in the deep layer of the forming cerebral cortex. At birth, granule cells in the cerebellum and glial cells of the olfactory bulb outer layer showed an SDF-1 in situ hybridization signal that decreased progressively within the next 2 weeks. In other regions such as cortex, thalamus and hippocampus, SDF-1 transcripts detected at birth progressively increased in abundance during the postnatal period. SDF-1 protein was identified by immunoblot and/or immunocytochemistry in most brain regions where these transcripts were detected. SDF-1 was selectively localized in some thalamic nuclei and neurons of the fifth cortical layer as well as in pontine and brainstem nuclei which relay the nociceptive response. The presence of SDF-1 transcripts in cerebellar granule cells was correlated with their migration from the external to the inner granular layers with disappearance of the signal when migration was completed. In contrast, SDF1 mRNA signal increased during formation of the hippocampal dentate gyrus and stayed high in this region throughout life. The selective and regulated expression of SDF-1 in these regions suggests a role in precursor migration, neurogenesis and, possibly, synaptogenesis. Thus this Alpha Chemokine may be as essential to nervous system function as it is to the immune system.
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Differential signalling of the Chemokine receptor CXCR4 by stromal cell-derived factor 1 and the HIV glycoprotein in rat neurons and astrocytes.
The European journal of neuroscience, 2000Co-Authors: Françoise Lazarini, To Nam Tham, Philippe Casanova, Erik De Clercq, Fernando Arenzana-seisdedos, Françoise Baleux, Monique Dubois-dalcqAbstract:CXCR4 is the Gi protein-linked seven-transmembrane receptor for the Alpha Chemokine stromal cell-derived factor 1 (SDF-1), a chemoattractant for lymphocytes. This receptor is highly conserved between human and rodent. CXCR4 is also a coreceptor for entry of human immunodeficiency virus (HIV) in T cells and is expressed in the CNS. To investigate how these CXCR4 ligands influence CNS development and/or function, we have examined the expression and signalling of this Chemokine receptor in rat neurons and astrocytes in vitro. CXCR4 transcripts and protein are synthesized by both cell types and in E15 brain neuronal progenitors. In these progenitors, SDF-1, but not gp120 (the HIV glycoprotein), induced activation of extracellular signal regulated kinases (ERKs) 1/2 and a dose-dependent chemotactic response. This chemotaxis was inhibited by Pertussis toxin, which uncouples Gi proteins and the bicyclam AMD3100, a highly selective CXCR4 antagonist, as well as by an inhibitor of the MAP kinase pathway. In differentiated neurons, both SDF-1 and the glycoprotein of HIV, gp120, triggered activation of ERKs with similar kinetics. These effects were significantly inhibited by Pertussis toxin and the CXCR4 antagonist. Rat astrocytes also responded to SDF-1 signalling by phosphorylation of ERKs but, in contrast to cortical neurons, no kinase activation was induced by gp120. Thus neurons and astrocytes can respond differently to signalling by SDF-1 and/or gp120. As SDF-1 triggers directed migration of neuronal progenitors, this Alpha Chemokine may play a role in cortex development. In differentiated neurons, both natural and viral ligands of CXCR4 activate ERKs and may therefore influence neuronal function.
To Nam Tham - One of the best experts on this subject based on the ideXlab platform.
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Differential signalling of the Chemokine receptor CXCR4 by stromal cell-derived factor 1 and the HIV glycoprotein in rat neurons and astrocytes.
European Journal of Neuroscience, 2008Co-Authors: Françoise Lazarini, To Nam Tham, Philippe Casanova, Erik De Clercq, Fernando Arenzana-seisdedos, Françoise Baleux, Monique Dubois-dalcqAbstract:: CXCR4 is the Gi protein-linked seven-transmembrane receptor for the Alpha Chemokine stromal cell-derived factor 1 (SDF-1), a chemoattractant for lymphocytes. This receptor is highly conserved between human and rodent. CXCR4 is also a coreceptor for entry of human immunodeficiency virus (HIV) in T cells and is expressed in the CNS. To investigate how these CXCR4 ligands influence CNS development and/or function, we have examined the expression and signalling of this Chemokine receptor in rat neurons and astrocytes in vitro. CXCR4 transcripts and protein are synthesized by both cell types and in E15 brain neuronal progenitors. In these progenitors, SDF-1, but not gp120 (the HIV glycoprotein), induced activation of extracellular signal regulated kinases (ERKs) 1/2 and a dose-dependent chemotactic response. This chemotaxis was inhibited by Pertussis toxin, which uncouples Gi proteins and the bicyclam AMD3100, a highly selective CXCR4 antagonist, as well as by an inhibitor of the MAP kinase pathway. In differentiated neurons, both SDF-1 and the glycoprotein of HIV, gp120, triggered activation of ERKs with similar kinetics. These effects were significantly inhibited by Pertussis toxin and the CXCR4 antagonist. Rat astrocytes also responded to SDF-1 signalling by phosphorylation of ERKs but, in contrast to cortical neurons, no kinase activation was induced by gp120. Thus neurons and astrocytes can respond differently to signalling by SDF-1 and/or gp120. As SDF-1 triggers directed migration of neuronal progenitors, this Alpha Chemokine may play a role in cortex development. In differentiated neurons, both natural and viral ligands of CXCR4 activate ERKs and may therefore influence neuronal function.
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Developmental pattern of expression of the Alpha Chemokine stromal cell‐derived factor 1 in the rat central nervous system
European Journal of Neuroscience, 2001Co-Authors: To Nam Tham, Françoise Lazarini, Isabelle Franceschini, François Lachapelle, Ali Amara, Monique Dubois-dalcqAbstract:: Stromal cell-derived factor 1 (SDF-1) is an Alpha-Chemokine that stimulates migration of haematopoietic progenitor cells and development of the immune system. SDF-1 is also abundantly and selectively expressed in the developing and mature CNS, as we show here. At embryonic day 15, SDF-1 transcripts were detected in the germinal periventricular zone and in the deep layer of the forming cerebral cortex. At birth, granule cells in the cerebellum and glial cells of the olfactory bulb outer layer showed an SDF-1 in situ hybridization signal that decreased progressively within the next 2 weeks. In other regions such as cortex, thalamus and hippocampus, SDF-1 transcripts detected at birth progressively increased in abundance during the postnatal period. SDF-1 protein was identified by immunoblot and/or immunocytochemistry in most brain regions where these transcripts were detected. SDF-1 was selectively localized in some thalamic nuclei and neurons of the fifth cortical layer as well as in pontine and brainstem nuclei which relay the nociceptive response. The presence of SDF-1 transcripts in cerebellar granule cells was correlated with their migration from the external to the inner granular layers with disappearance of the signal when migration was completed. In contrast, SDF1 mRNA signal increased during formation of the hippocampal dentate gyrus and stayed high in this region throughout life. The selective and regulated expression of SDF-1 in these regions suggests a role in precursor migration, neurogenesis and, possibly, synaptogenesis. Thus this Alpha Chemokine may be as essential to nervous system function as it is to the immune system.
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developmental pattern of expression of the Alpha Chemokine stromal cell derived factor 1 in the rat central nervous system
European Journal of Neuroscience, 2001Co-Authors: To Nam Tham, Françoise Lazarini, Isabelle Franceschini, François Lachapelle, Ali Amara, Monique DuboisdalcqAbstract:Stromal cell-derived factor 1 (SDF-1) is an Alpha-Chemokine that stimulates migration of haematopoietic progenitor cells and development of the immune system. SDF-1 is also abundantly and selectively expressed in the developing and mature CNS, as we show here. At embryonic day 15, SDF-1 transcripts were detected in the germinal periventricular zone and in the deep layer of the forming cerebral cortex. At birth, granule cells in the cerebellum and glial cells of the olfactory bulb outer layer showed an SDF-1 in situ hybridization signal that decreased progressively within the next 2 weeks. In other regions such as cortex, thalamus and hippocampus, SDF-1 transcripts detected at birth progressively increased in abundance during the postnatal period. SDF-1 protein was identified by immunoblot and/or immunocytochemistry in most brain regions where these transcripts were detected. SDF-1 was selectively localized in some thalamic nuclei and neurons of the fifth cortical layer as well as in pontine and brainstem nuclei which relay the nociceptive response. The presence of SDF-1 transcripts in cerebellar granule cells was correlated with their migration from the external to the inner granular layers with disappearance of the signal when migration was completed. In contrast, SDF1 mRNA signal increased during formation of the hippocampal dentate gyrus and stayed high in this region throughout life. The selective and regulated expression of SDF-1 in these regions suggests a role in precursor migration, neurogenesis and, possibly, synaptogenesis. Thus this Alpha Chemokine may be as essential to nervous system function as it is to the immune system.
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Differential signalling of the Chemokine receptor CXCR4 by stromal cell-derived factor 1 and the HIV glycoprotein in rat neurons and astrocytes.
The European journal of neuroscience, 2000Co-Authors: Françoise Lazarini, To Nam Tham, Philippe Casanova, Erik De Clercq, Fernando Arenzana-seisdedos, Françoise Baleux, Monique Dubois-dalcqAbstract:CXCR4 is the Gi protein-linked seven-transmembrane receptor for the Alpha Chemokine stromal cell-derived factor 1 (SDF-1), a chemoattractant for lymphocytes. This receptor is highly conserved between human and rodent. CXCR4 is also a coreceptor for entry of human immunodeficiency virus (HIV) in T cells and is expressed in the CNS. To investigate how these CXCR4 ligands influence CNS development and/or function, we have examined the expression and signalling of this Chemokine receptor in rat neurons and astrocytes in vitro. CXCR4 transcripts and protein are synthesized by both cell types and in E15 brain neuronal progenitors. In these progenitors, SDF-1, but not gp120 (the HIV glycoprotein), induced activation of extracellular signal regulated kinases (ERKs) 1/2 and a dose-dependent chemotactic response. This chemotaxis was inhibited by Pertussis toxin, which uncouples Gi proteins and the bicyclam AMD3100, a highly selective CXCR4 antagonist, as well as by an inhibitor of the MAP kinase pathway. In differentiated neurons, both SDF-1 and the glycoprotein of HIV, gp120, triggered activation of ERKs with similar kinetics. These effects were significantly inhibited by Pertussis toxin and the CXCR4 antagonist. Rat astrocytes also responded to SDF-1 signalling by phosphorylation of ERKs but, in contrast to cortical neurons, no kinase activation was induced by gp120. Thus neurons and astrocytes can respond differently to signalling by SDF-1 and/or gp120. As SDF-1 triggers directed migration of neuronal progenitors, this Alpha Chemokine may play a role in cortex development. In differentiated neurons, both natural and viral ligands of CXCR4 activate ERKs and may therefore influence neuronal function.
Bradford A. Navia - One of the best experts on this subject based on the ideXlab platform.
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Tumor necrosis factor Alpha leads to increased cell surface expression of CXCR4 in SK-N-MC cells.
Journal of NeuroVirology, 2005Co-Authors: Kevin Rostasy, Gullue Gorgun, Yelena Kleyner, Anthony Garcia, Michael L. Kramer, Suzanne Melanson, Jean Marie Mathys, Constantin T. Yiannoutsos, Paul R. Skolnik, Bradford A. NaviaAbstract:Both host and viral factors play an important role in the pathogenesis of human immunodeficiency virus (HIV)-associated bran injury. In this study, the authors examined the interactions between tumor necrosis factor (TNF)-α, CXCR4, the Alpha Chemokine receptor, and three HIV isolates, including the T-tropic viruses, HIV-1MN and HIV-1IIIB, and the dual tropic virus, HIV-189.6. The authors show by flow cytometry that treatment of differentiated SK-N-MC cells with TNF-α induces a significant increase in the cell surface expression of CXCR4 in a time- and dose-dependent manner. The effect is partly regulated at the level of transcription. To assess the biological significance of this finding, we show that TNF-α potentiates the ability of the above mentioned HIV isolates to induce neuronal apoptosis and that the effect is significantly reduced by pretreating cells with monoclonal antibodies to either CXCR4 and TNF-α. Together these results suggest that TNF-α may render neuronal cells vulnerable to the apoptoti...
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Tumor necrosis factor Alpha leads to increased cell surface expression of CXCR4 in SK-N-MC cells
Journal of NeuroVirology, 2005Co-Authors: Kevin Rostasy, Gullue Gorgun, Yelena Kleyner, Anthony Garcia, Suzanne Melanson, Jean Marie Mathys, Constantin T. Yiannoutsos, Paul R. Skolnik, Michael Kramer, Bradford A. NaviaAbstract:Both host and viral factors play an important role in the pathogenesis of human immunodeficiency virus (HIV)-associated bran injury. In this study, the authors examined the interactions between tumor necrosis factor (TNF)-α, CXCR4, the Alpha Chemokine receptor, and three HIV isolates, including the T-tropic viruses, HIV-1_MN and HIV-1_IIIB, and the dual tropic virus, HIV-1_89.6. The authors show by flow cytometry that treatment of differentiated SK-N-MC cells with TNF-α induces a significant increase in the cell surface expression of CXCR4 in a time- and dose-dependent manner. The effect is partly regulated at the level of transcription. To assess the biological significance of this finding, we show that TNF-α potentiates the ability of the above mentioned HIV isolates to induce neuronal apoptosis and that the effect is significantly reduced by pretreating cells with monoclonal antibodies to either CXCR4 and TNF-α. Together these results suggest that TNF-α may render neuronal cells vulnerable to the apoptotic effects of HIV by increasing the cell surface expression of CXCR4 and thus identify another mechanism by which TNF-α contributes to the pathogenesis of HIV-associated brain injury.
