Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration

Inflammation-mediated neurodegeneration occurs in the acute and the chronic phases of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Classically activated (M1) microglia are key players mediating this process. Here, we identified Galectin-1 (Gal1), an...

Descripción completa

Detalles Bibliográficos
Autores principales:	Hernández, Silvia Fatima, Croci Russo, Diego Omar
Publicado:	2012
Materias:	CD45 antigen CD86 antigen cyclic AMP responsive element binding protein galectin 1 gamma interferon glycan immunoglobulin enhancer binding protein inducible nitric oxide synthase interleukin 17 interleukin 4 major histocompatibility antigen class 2 mitogen activated protein kinase p38 monocyte chemotactic protein 1 phosphatase recombinant galectin 1 recombinant protein transforming growth factor beta1 tumor necrosis factor unclassified drug acute phase response adoptive transfer allergic encephalomyelitis animal cell animal experiment animal model animal tissue antiinflammatory activity article astrocyte cell surface central nervous system controlled study demyelination enzyme activation enzyme activity female flow cytometry inflammation macrophage activation microglia mouse nerve degeneration neuropathy neuroprotection neurotoxicity newborn nonhuman priority journal protein binding protein carbohydrate interaction protein expression protein function signal transduction Animals Antigens, CD45 Astrocytes Central Nervous System Chemokine CCL2 Cyclic AMP Response Element-Binding Protein Encephalomyelitis, Autoimmune, Experimental Female Galectin 1 Humans Interleukin-6 Mice Mice, Inbred C57BL Mice, Knockout Microglia Multiple Sclerosis NF-kappa B Nitric Oxide Synthase Type II p38 Mitogen-Activated Protein Kinases Polysaccharides Protein Binding Tumor Necrosis Factor-alpha
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10747613_v37_n2_p249_Starossom http://hdl.handle.net/20.500.12110/paper_10747613_v37_n2_p249_Starossom
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_10747613_v37_n2_p249_Starossom
record_format	dspace
spelling	paper:paper_10747613_v37_n2_p249_Starossom2023-06-08T16:05:10Z Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration Hernández, Silvia Fatima Croci Russo, Diego Omar CD45 antigen CD86 antigen cyclic AMP responsive element binding protein galectin 1 gamma interferon glycan immunoglobulin enhancer binding protein inducible nitric oxide synthase interleukin 17 interleukin 4 major histocompatibility antigen class 2 mitogen activated protein kinase p38 monocyte chemotactic protein 1 phosphatase recombinant galectin 1 recombinant protein transforming growth factor beta1 tumor necrosis factor unclassified drug acute phase response adoptive transfer allergic encephalomyelitis animal cell animal experiment animal model animal tissue antiinflammatory activity article astrocyte cell surface central nervous system controlled study demyelination enzyme activation enzyme activity female flow cytometry inflammation macrophage activation microglia mouse nerve degeneration neuropathy neuroprotection neurotoxicity newborn nonhuman priority journal protein binding protein carbohydrate interaction protein expression protein function signal transduction Animals Antigens, CD45 Astrocytes Central Nervous System Chemokine CCL2 Cyclic AMP Response Element-Binding Protein Encephalomyelitis, Autoimmune, Experimental Female Galectin 1 Humans Interleukin-6 Mice Mice, Inbred C57BL Mice, Knockout Microglia Multiple Sclerosis NF-kappa B Nitric Oxide Synthase Type II p38 Mitogen-Activated Protein Kinases Polysaccharides Protein Binding Tumor Necrosis Factor-alpha Inflammation-mediated neurodegeneration occurs in the acute and the chronic phases of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Classically activated (M1) microglia are key players mediating this process. Here, we identified Galectin-1 (Gal1), an endogenous glycan-binding protein, as a pivotal regulator of M1 microglial activation that targets the activation of p38MAPK-, CREB-, and NF-κB-dependent signaling pathways and hierarchically suppresses downstream proinflammatory mediators, such as iNOS, TNF, and CCL2. Gal1 bound to core 2 O-glycans on CD45, favoring retention of this glycoprotein on the microglial cell surface and augmenting its phosphatase activity and inhibitory function. Gal1 was highly expressed in the acute phase of EAE, and its targeted deletion resulted in pronounced inflammation-induced neurodegeneration. Adoptive transfer of Gal1-secreting astrocytes or administration of recombinant Gal1 suppressed EAE through mechanisms involving microglial deactivation. Thus, Gal1-glycan interactions are essential in tempering microglial activation, brain inflammation, and neurodegeneration, with critical therapeutic implications for MS. © 2012 Elsevier Inc. Fil:Hernandez, S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Croci, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10747613_v37_n2_p249_Starossom http://hdl.handle.net/20.500.12110/paper_10747613_v37_n2_p249_Starossom
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	CD45 antigen CD86 antigen cyclic AMP responsive element binding protein galectin 1 gamma interferon glycan immunoglobulin enhancer binding protein inducible nitric oxide synthase interleukin 17 interleukin 4 major histocompatibility antigen class 2 mitogen activated protein kinase p38 monocyte chemotactic protein 1 phosphatase recombinant galectin 1 recombinant protein transforming growth factor beta1 tumor necrosis factor unclassified drug acute phase response adoptive transfer allergic encephalomyelitis animal cell animal experiment animal model animal tissue antiinflammatory activity article astrocyte cell surface central nervous system controlled study demyelination enzyme activation enzyme activity female flow cytometry inflammation macrophage activation microglia mouse nerve degeneration neuropathy neuroprotection neurotoxicity newborn nonhuman priority journal protein binding protein carbohydrate interaction protein expression protein function signal transduction Animals Antigens, CD45 Astrocytes Central Nervous System Chemokine CCL2 Cyclic AMP Response Element-Binding Protein Encephalomyelitis, Autoimmune, Experimental Female Galectin 1 Humans Interleukin-6 Mice Mice, Inbred C57BL Mice, Knockout Microglia Multiple Sclerosis NF-kappa B Nitric Oxide Synthase Type II p38 Mitogen-Activated Protein Kinases Polysaccharides Protein Binding Tumor Necrosis Factor-alpha
spellingShingle	CD45 antigen CD86 antigen cyclic AMP responsive element binding protein galectin 1 gamma interferon glycan immunoglobulin enhancer binding protein inducible nitric oxide synthase interleukin 17 interleukin 4 major histocompatibility antigen class 2 mitogen activated protein kinase p38 monocyte chemotactic protein 1 phosphatase recombinant galectin 1 recombinant protein transforming growth factor beta1 tumor necrosis factor unclassified drug acute phase response adoptive transfer allergic encephalomyelitis animal cell animal experiment animal model animal tissue antiinflammatory activity article astrocyte cell surface central nervous system controlled study demyelination enzyme activation enzyme activity female flow cytometry inflammation macrophage activation microglia mouse nerve degeneration neuropathy neuroprotection neurotoxicity newborn nonhuman priority journal protein binding protein carbohydrate interaction protein expression protein function signal transduction Animals Antigens, CD45 Astrocytes Central Nervous System Chemokine CCL2 Cyclic AMP Response Element-Binding Protein Encephalomyelitis, Autoimmune, Experimental Female Galectin 1 Humans Interleukin-6 Mice Mice, Inbred C57BL Mice, Knockout Microglia Multiple Sclerosis NF-kappa B Nitric Oxide Synthase Type II p38 Mitogen-Activated Protein Kinases Polysaccharides Protein Binding Tumor Necrosis Factor-alpha Hernández, Silvia Fatima Croci Russo, Diego Omar Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration
topic_facet	CD45 antigen CD86 antigen cyclic AMP responsive element binding protein galectin 1 gamma interferon glycan immunoglobulin enhancer binding protein inducible nitric oxide synthase interleukin 17 interleukin 4 major histocompatibility antigen class 2 mitogen activated protein kinase p38 monocyte chemotactic protein 1 phosphatase recombinant galectin 1 recombinant protein transforming growth factor beta1 tumor necrosis factor unclassified drug acute phase response adoptive transfer allergic encephalomyelitis animal cell animal experiment animal model animal tissue antiinflammatory activity article astrocyte cell surface central nervous system controlled study demyelination enzyme activation enzyme activity female flow cytometry inflammation macrophage activation microglia mouse nerve degeneration neuropathy neuroprotection neurotoxicity newborn nonhuman priority journal protein binding protein carbohydrate interaction protein expression protein function signal transduction Animals Antigens, CD45 Astrocytes Central Nervous System Chemokine CCL2 Cyclic AMP Response Element-Binding Protein Encephalomyelitis, Autoimmune, Experimental Female Galectin 1 Humans Interleukin-6 Mice Mice, Inbred C57BL Mice, Knockout Microglia Multiple Sclerosis NF-kappa B Nitric Oxide Synthase Type II p38 Mitogen-Activated Protein Kinases Polysaccharides Protein Binding Tumor Necrosis Factor-alpha
description	Inflammation-mediated neurodegeneration occurs in the acute and the chronic phases of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Classically activated (M1) microglia are key players mediating this process. Here, we identified Galectin-1 (Gal1), an endogenous glycan-binding protein, as a pivotal regulator of M1 microglial activation that targets the activation of p38MAPK-, CREB-, and NF-κB-dependent signaling pathways and hierarchically suppresses downstream proinflammatory mediators, such as iNOS, TNF, and CCL2. Gal1 bound to core 2 O-glycans on CD45, favoring retention of this glycoprotein on the microglial cell surface and augmenting its phosphatase activity and inhibitory function. Gal1 was highly expressed in the acute phase of EAE, and its targeted deletion resulted in pronounced inflammation-induced neurodegeneration. Adoptive transfer of Gal1-secreting astrocytes or administration of recombinant Gal1 suppressed EAE through mechanisms involving microglial deactivation. Thus, Gal1-glycan interactions are essential in tempering microglial activation, brain inflammation, and neurodegeneration, with critical therapeutic implications for MS. © 2012 Elsevier Inc.
author	Hernández, Silvia Fatima Croci Russo, Diego Omar
author_facet	Hernández, Silvia Fatima Croci Russo, Diego Omar
author_sort	Hernández, Silvia Fatima
title	Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration
title_short	Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration
title_full	Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration
title_fullStr	Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration
title_full_unstemmed	Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration
title_sort	galectin-1 deactivates classically activated microglia and protects from inflammation-induced neurodegeneration
publishDate	2012
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10747613_v37_n2_p249_Starossom http://hdl.handle.net/20.500.12110/paper_10747613_v37_n2_p249_Starossom
work_keys_str_mv	AT hernandezsilviafatima galectin1deactivatesclassicallyactivatedmicrogliaandprotectsfrominflammationinducedneurodegeneration AT crocirussodiegoomar galectin1deactivatesclassicallyactivatedmicrogliaandprotectsfrominflammationinducedneurodegeneration
_version_	1768542188894945280

Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration

Ejemplares similares