Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3389/fphar.2020.00161 http://hdl.handle.net/11449/200231 |
Resumo: | Multiple sclerosis (MS) is a progressive disease of the central nervous system (CNS) that involves damage to the myelin sheath surrounding axons. MS therapy is based on immunomodulatory drugs that reduce disease recurrence and severity. Vitamin D is a hormone whose immunomodulatory ability has been widely demonstrated, including in experimental autoimmune encephalomyelitis (EAE), which is an animal model of CNS inflammation. In this study, we evaluated the potential of very early intervention with the active form of vitamin D (1,25-dihydroxyvitamin D3) to control neuroinflammation during EAE development. EAE was induced in C57BL/6J mice and 1,25-dihydroxyvitamin D3 administration began 1 day after disease induction. This procedure decreased prevalence, clinical score, inflammation, and demyelination. It also reduced MHCII expression in macrophages and microglia as well as the level of oxidative stress and messenger RNA (mRNA) expression for NLRP3, caspase-1, interleukin (IL)-1β, CX3CR1, CCL17, RORc and Tbx21 at the CNS. Otherwise, mRNA expression for ZO-1 increased at the lumbar spinal cord. These effects were accompanied by the stabilization of blood-spinal cord barrier permeability. The results of this study indicate that early intervention with 1,25-dihydroxyvitamin D3 can control the neuroinflammatory process that is the hallmark of EAE and MS immunopathogenesis and should thus be explored as an adjunct therapy for MS patients. |
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Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation1,25-dihydroxyvitamin D3blood-brain barrierexperimental autoimmune encephalomyelitisinflammasomeoxidative stressMultiple sclerosis (MS) is a progressive disease of the central nervous system (CNS) that involves damage to the myelin sheath surrounding axons. MS therapy is based on immunomodulatory drugs that reduce disease recurrence and severity. Vitamin D is a hormone whose immunomodulatory ability has been widely demonstrated, including in experimental autoimmune encephalomyelitis (EAE), which is an animal model of CNS inflammation. In this study, we evaluated the potential of very early intervention with the active form of vitamin D (1,25-dihydroxyvitamin D3) to control neuroinflammation during EAE development. EAE was induced in C57BL/6J mice and 1,25-dihydroxyvitamin D3 administration began 1 day after disease induction. This procedure decreased prevalence, clinical score, inflammation, and demyelination. It also reduced MHCII expression in macrophages and microglia as well as the level of oxidative stress and messenger RNA (mRNA) expression for NLRP3, caspase-1, interleukin (IL)-1β, CX3CR1, CCL17, RORc and Tbx21 at the CNS. Otherwise, mRNA expression for ZO-1 increased at the lumbar spinal cord. These effects were accompanied by the stabilization of blood-spinal cord barrier permeability. The results of this study indicate that early intervention with 1,25-dihydroxyvitamin D3 can control the neuroinflammatory process that is the hallmark of EAE and MS immunopathogenesis and should thus be explored as an adjunct therapy for MS patients.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Tropical Diseases Botucatu Medical School São Paulo State University (UNESP)Department of Microbiology and Immunology Institute of Biosciences São Paulo State University (UNESP)Department of Chemistry and Biochemistry Institute of Biosciences São Paulo State University (UNESP)Department of Tropical Diseases Botucatu Medical School São Paulo State University (UNESP)Department of Microbiology and Immunology Institute of Biosciences São Paulo State University (UNESP)Department of Chemistry and Biochemistry Institute of Biosciences São Paulo State University (UNESP)Universidade Estadual Paulista (Unesp)de Oliveira, Larissa Ragozo Cardoso [UNESP]Mimura, Luiza Ayumi Nishiyama [UNESP]Fraga-Silva, Thais Fernanda de Campos [UNESP]Ishikawa, Larissa Lumi Watanabe [UNESP]Fernandes, Ana Angélica Henrique [UNESP]Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP]Sartori, Alexandrina [UNESP]2020-12-12T02:01:05Z2020-12-12T02:01:05Z2020-03-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fphar.2020.00161Frontiers in Pharmacology, v. 11.1663-9812http://hdl.handle.net/11449/20023110.3389/fphar.2020.001612-s2.0-85082698310Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers in Pharmacologyinfo:eu-repo/semantics/openAccess2024-08-15T15:22:32Zoai:repositorio.unesp.br:11449/200231Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-15T15:22:32Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation |
title |
Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation |
spellingShingle |
Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation de Oliveira, Larissa Ragozo Cardoso [UNESP] 1,25-dihydroxyvitamin D3 blood-brain barrier experimental autoimmune encephalomyelitis inflammasome oxidative stress |
title_short |
Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation |
title_full |
Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation |
title_fullStr |
Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation |
title_full_unstemmed |
Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation |
title_sort |
Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation |
author |
de Oliveira, Larissa Ragozo Cardoso [UNESP] |
author_facet |
de Oliveira, Larissa Ragozo Cardoso [UNESP] Mimura, Luiza Ayumi Nishiyama [UNESP] Fraga-Silva, Thais Fernanda de Campos [UNESP] Ishikawa, Larissa Lumi Watanabe [UNESP] Fernandes, Ana Angélica Henrique [UNESP] Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP] Sartori, Alexandrina [UNESP] |
author_role |
author |
author2 |
Mimura, Luiza Ayumi Nishiyama [UNESP] Fraga-Silva, Thais Fernanda de Campos [UNESP] Ishikawa, Larissa Lumi Watanabe [UNESP] Fernandes, Ana Angélica Henrique [UNESP] Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP] Sartori, Alexandrina [UNESP] |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
de Oliveira, Larissa Ragozo Cardoso [UNESP] Mimura, Luiza Ayumi Nishiyama [UNESP] Fraga-Silva, Thais Fernanda de Campos [UNESP] Ishikawa, Larissa Lumi Watanabe [UNESP] Fernandes, Ana Angélica Henrique [UNESP] Zorzella-Pezavento, Sofia Fernanda Gonçalves [UNESP] Sartori, Alexandrina [UNESP] |
dc.subject.por.fl_str_mv |
1,25-dihydroxyvitamin D3 blood-brain barrier experimental autoimmune encephalomyelitis inflammasome oxidative stress |
topic |
1,25-dihydroxyvitamin D3 blood-brain barrier experimental autoimmune encephalomyelitis inflammasome oxidative stress |
description |
Multiple sclerosis (MS) is a progressive disease of the central nervous system (CNS) that involves damage to the myelin sheath surrounding axons. MS therapy is based on immunomodulatory drugs that reduce disease recurrence and severity. Vitamin D is a hormone whose immunomodulatory ability has been widely demonstrated, including in experimental autoimmune encephalomyelitis (EAE), which is an animal model of CNS inflammation. In this study, we evaluated the potential of very early intervention with the active form of vitamin D (1,25-dihydroxyvitamin D3) to control neuroinflammation during EAE development. EAE was induced in C57BL/6J mice and 1,25-dihydroxyvitamin D3 administration began 1 day after disease induction. This procedure decreased prevalence, clinical score, inflammation, and demyelination. It also reduced MHCII expression in macrophages and microglia as well as the level of oxidative stress and messenger RNA (mRNA) expression for NLRP3, caspase-1, interleukin (IL)-1β, CX3CR1, CCL17, RORc and Tbx21 at the CNS. Otherwise, mRNA expression for ZO-1 increased at the lumbar spinal cord. These effects were accompanied by the stabilization of blood-spinal cord barrier permeability. The results of this study indicate that early intervention with 1,25-dihydroxyvitamin D3 can control the neuroinflammatory process that is the hallmark of EAE and MS immunopathogenesis and should thus be explored as an adjunct therapy for MS patients. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-12T02:01:05Z 2020-12-12T02:01:05Z 2020-03-12 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3389/fphar.2020.00161 Frontiers in Pharmacology, v. 11. 1663-9812 http://hdl.handle.net/11449/200231 10.3389/fphar.2020.00161 2-s2.0-85082698310 |
url |
http://dx.doi.org/10.3389/fphar.2020.00161 http://hdl.handle.net/11449/200231 |
identifier_str_mv |
Frontiers in Pharmacology, v. 11. 1663-9812 10.3389/fphar.2020.00161 2-s2.0-85082698310 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Frontiers in Pharmacology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1808128122246135808 |