Preclinical Therapy with Vitamin D3 in Experimental Encephalomyelitis: Efficacy and Comparison with Paricalcitol

Author(s)

Mimura, Luiza Ayumi Nishiyama ^[1] ; Fraga-Silva, Thais Fernanda de Campos ^[1] ; Oliveira, Larissa Ragozzo Cardoso de ^[1] ; Ishikawa, Larissa Lumi Watanabe ^[1] ; Borim, Patricia Aparecida ^[2] ; Machado, Carla de Moraes ^[3] ; Junior, Jose de Anchieta de Castro e Horta ^[3] ; Fonseca, Denise Morais da ^[4] ; Sartori, Alexandrina ^[1]

Affiliation

^[1] Sao Paulo State Univ Unesp, Inst Biosci, Dept Chem & Biol Sci, BR-18618689 Botucatu, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Dept Trop Dis & Image Diag, Botucatu Med Sch, BR-18618687 Botucatu, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Inst Biosci, Dept Struct & Funct Biol, BR-18618689 Botucatu, SP - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508000 Sao Paulo - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 4 FEB 2021.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 15/06706-8 - Vitamin D, paricalcitol, glibenclamide and clofazimine: therapeutic and immunomodulatory potential in experimental autoimmune encephalomyelitis
• Grantee: Luiza Ayumi Nishiyama Mimura
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/26257-8 - Tolerogenic efficacy of the association MOG/vitamin D analog or MOG/rapamycin on experimental autoimmune encephalomyelitis
• Grantee: Alexandrina Sartori
• Support Opportunities: Regular Research Grants