Calcitriol Prevents Neuroinflammation and Reduces Blood-Brain Barrier Disruption and Local Macrophage/Microglia Activation

Detalhes bibliográficos
Autor(a) principal: de Oliveira, Larissa Ragozo Cardoso [UNESP]
Data de Publicação: 2020
Outros Autores: 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]
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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spelling 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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