Preclinical therapy with vitamin d3 in experimental encephalomyelitis: Efficacy and comparison with paricalcitol

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dc.contributor.authorMimura, Luiza Ayumi Nishiyama [UNESP]
dc.contributor.authorde Campos Fraga-Silva, Thais Fernanda [UNESP]
dc.contributor.authorde Oliveira, Larissa Ragozzo Cardoso [UNESP]
dc.contributor.authorIshikawa, Larissa Lumi Watanabe [UNESP]
dc.contributor.authorBorim, Patrícia Aparecida [UNESP]
dc.contributor.authorMachado, Carla de Moraes [UNESP]
dc.contributor.authorJúnior, José de Anchieta de Castro e Horta [UNESP]
dc.contributor.authorda Fonseca, Denise Morais
dc.contributor.authorSartori, Alexandrina [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2021-06-25T10:52:27Z
dc.date.available2021-06-25T10:52:27Z
dc.date.issued2021-02-02
dc.description.abstractMultiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). MS and its animal model called experimental autoimmune encephalomyelitis (EAE) immunopathogenesis involve a plethora of immune cells whose activation releases a variety of proinflammatory mediators and free radicals. Vitamin D3 (VitD) is endowed with immunomodulatory and antioxidant properties that we demonstrated to control EAE development. However, this protective effect triggered hypercalcemia. As such, we compared the therapeutic potential of VitD and paricalcitol (Pari), which is a non-hypercalcemic vitamin D analog, to control EAE. From the seventh day on after EAE induction, mice were injected with VitD or Pari every other day. VitD, but not Pari, displayed downmodulatory ability being able to reduce the recruitment of inflammatory cells, the mRNA expression of inflammatory parameters, and demyelination at the CNS. Lower production of proinflammatory cytokines by lymph node-derived cells and IL-17 by gut explants, and reduced intestinal inflammation were detected in the EAE/VitD group compared to the EAE untreated or Pari groups. Dendritic cells (DCs) differentiated in the presence of VitD developed a more tolerogenic phenotype than in the presence of Pari. These findings suggest that VitD, but not Pari, has the potential to be used as a preventive therapy to control MS severity.en
dc.description.affiliationDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)
dc.description.affiliationBotucatu Medical School Department of Tropical Diseases and Image Diagnosis São Paulo State University (UNESP)
dc.description.affiliationDepartment of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP)
dc.description.affiliationDepartment of Immunology Institute of Biomedical Sciences University of Sao Paulo (USP)
dc.description.affiliationUnespDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP)
dc.description.affiliationUnespBotucatu Medical School Department of Tropical Diseases and Image Diagnosis São Paulo State University (UNESP)
dc.description.affiliationUnespDepartment of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdFAPESP: 2013/26257-8
dc.description.sponsorshipIdFAPESP: 2015/06706-8
dc.description.sponsorshipIdCNPq: 307269/2017-5
dc.format.extent1-21
dc.identifierhttp://dx.doi.org/10.3390/ijms22041914
dc.identifier.citationInternational Journal of Molecular Sciences, v. 22, n. 4, p. 1-21, 2021.
dc.identifier.doi10.3390/ijms22041914
dc.identifier.issn1422-0067
dc.identifier.issn1661-6596
dc.identifier.scopus2-s2.0-85100829329
dc.identifier.urihttp://hdl.handle.net/11449/207282
dc.language.isoeng
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.sourceScopus
dc.subjectDendritic cells
dc.subjectExperimental autoimmune encephalomyelitis
dc.subjectGut
dc.subjectInflammation
dc.subjectParicalcitol
dc.subjectVitamin D analog
dc.subjectVitamin D3
dc.titlePreclinical therapy with vitamin d3 in experimental encephalomyelitis: Efficacy and comparison with paricalcitolen
dc.typeArtigo

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