PMID- 33671896
OWN - NLM
STAT- MEDLINE
DCOM- 20210423
LR  - 20210423
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 4
DP  - 2021 Feb 15
TI  - Preclinical Therapy with Vitamin D3 in Experimental Encephalomyelitis: Efficacy 
      and Comparison with Paricalcitol.
LID - 10.3390/ijms22041914 [doi]
LID - 1914
AB  - Multiple 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.
FAU - Mimura, Luiza Ayumi Nishiyama
AU  - Mimura LAN
AD  - Department of Chemical and Biological Sciences, Institute of Biosciences, Sao 
      Paulo State University (UNESP), Botucatu 18618-689, Brazil.
FAU - Fraga-Silva, Thais Fernanda de Campos
AU  - Fraga-Silva TFC
AUID- ORCID: 0000-0002-2053-8938
AD  - Department of Chemical and Biological Sciences, Institute of Biosciences, Sao 
      Paulo State University (UNESP), Botucatu 18618-689, Brazil.
FAU - Oliveira, Larissa Ragozzo Cardoso de
AU  - Oliveira LRC
AD  - Department of Chemical and Biological Sciences, Institute of Biosciences, Sao 
      Paulo State University (UNESP), Botucatu 18618-689, Brazil.
FAU - Ishikawa, Larissa Lumi Watanabe
AU  - Ishikawa LLW
AUID- ORCID: 0000-0003-3481-2181
AD  - Department of Chemical and Biological Sciences, Institute of Biosciences, Sao 
      Paulo State University (UNESP), Botucatu 18618-689, Brazil.
FAU - Borim, Patricia Aparecida
AU  - Borim PA
AD  - Botucatu Medical School, Department of Tropical Diseases and Image Diagnosis, Sao 
      Paulo State University (UNESP), Botucatu 18618-687, Brazil.
FAU - Machado, Carla de Moraes
AU  - Machado CM
AD  - Department of Structural and Functional Biology, Institute of Biosciences, Sao 
      Paulo State University (UNESP), Botucatu 18618-689, Brazil.
FAU - Junior, Jose de Anchieta de Castro E Horta
AU  - Junior JACEH
AUID- ORCID: 0000-0003-3639-9861
AD  - Department of Structural and Functional Biology, Institute of Biosciences, Sao 
      Paulo State University (UNESP), Botucatu 18618-689, Brazil.
FAU - Fonseca, Denise Morais da
AU  - Fonseca DMD
AD  - Department of Immunology, Institute of Biomedical Sciences, University of Sao 
      Paulo (USP), Sao Paulo 05508-000, Brazil.
FAU - Sartori, Alexandrina
AU  - Sartori A
AD  - Department of Chemical and Biological Sciences, Institute of Biosciences, Sao 
      Paulo State University (UNESP), Botucatu 18618-689, Brazil.
LA  - eng
GR  - 2016/23317-8/Fundacao de Amparo a Pesquisa do Estado de Sao Paulo/
GR  - 307269/2017-5/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/
PT  - Comparative Study
PT  - Journal Article
DEP - 20210215
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antioxidants)
RN  - 0 (Cytokines)
RN  - 0 (Ergocalciferols)
RN  - 0 (Immunologic Factors)
RN  - 1C6V77QF41 (Cholecalciferol)
RN  - 6702D36OG5 (paricalcitol)
SB  - IM
MH  - Animals
MH  - Antioxidants/*administration & dosage/pharmacology
MH  - Bone Marrow Cells/drug effects/immunology
MH  - Cholecalciferol/*administration & dosage/pharmacology
MH  - Cytokines/metabolism
MH  - Dendritic Cells/drug effects/immunology
MH  - Encephalomyelitis, Autoimmune, Experimental/blood/immunology/*prevention & 
      control
MH  - Ergocalciferols/*administration & dosage/pharmacology
MH  - Female
MH  - Immunologic Factors/*administration & dosage/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Multiple Sclerosis/immunology/prevention & control
MH  - Post-Exposure Prophylaxis/*methods
MH  - Severity of Illness Index
MH  - Signal Transduction/drug effects
MH  - Treatment Outcome
PMC - PMC7918993
OTO - NOTNLM
OT  - dendritic cells
OT  - experimental autoimmune encephalomyelitis
OT  - gut
OT  - inflammation
OT  - paricalcitol
OT  - vitamin D analog
OT  - vitamin D3
COIS- The authors declare no conflict of interest.
EDAT- 2021/03/07 06:00
MHDA- 2021/04/24 06:00
PMCR- 2021/02/15
CRDT- 2021/03/06 01:11
PHST- 2020/12/16 00:00 [received]
PHST- 2021/02/04 00:00 [revised]
PHST- 2021/02/07 00:00 [accepted]
PHST- 2021/03/06 01:11 [entrez]
PHST- 2021/03/07 06:00 [pubmed]
PHST- 2021/04/24 06:00 [medline]
PHST- 2021/02/15 00:00 [pmc-release]
AID - ijms22041914 [pii]
AID - ijms-22-01914 [pii]
AID - 10.3390/ijms22041914 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Feb 15;22(4):1914. doi: 10.3390/ijms22041914.