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Vitamin D, paricalcitol, glibenclamide and clofazimine: therapeutic and immunomodulatory potential in experimental autoimmune encephalomyelitis

Grant number: 15/06706-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2016
Effective date (End): February 28, 2019
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Alexandrina Sartori
Grantee:Luiza Ayumi Nishiyama Mimura
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Multiple sclerosis (MS) is a chronic and demyelinating disease of the central nervous system (CNS). MS immunophatogenesis involves Th1, Th17 and Tc autoreactive lymphocytes and also macrophages and microglial cells activation that release many pro-inflammatory mediators and free radicals. Current therapies do not determine disease cure and some subjects are refractory to therapies. Therefore, new alternatives need to be explored. The aim of this project is to investigate the therapeutic and immunododulatory effect of vitamin D3, paricalcitol, glibenclamide and clofazimine in the progression of experimental autoimmune encephalitis (EAE). In vitro experiments will initially be performed to determine the immunomodulatory potential of these substances. We will investigate the effect on pro-and anti-inflammatory cytokines in peritoneal macrophages, spleen cells and microglia (BV-2 strain) cultures. In vivo experiments will be performed in C57BL/6 mice treated with vitamin D3, paricalcitol or glibenclamide in different moments (after the EAE induction, in the early phase and after the first symptoms) to characterize its peripheral and local (SNC) immunomodulatory effects. The clofazimine therapeutic effect will be evaluated in the SJL mice, in the phase of disease reactivation. Most of the evaluations will be done with standard methods already used in the laboratory: ELISA (cytokines), real time PCR/Cytometry (cells subpopulations/phenotype and inflammasome), histopathology (CNS inflammatory infiltration/demyelination) and biochemical tests (oxidative stress).

Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MIMURA, Luiza Ayumi Nishiyama. Efeito terapêutico diferencial da vitamina D3 e do análogo Paricalcitol no desenvolvimento da EAE. 2019. Doctoral Thesis - Universidade Estadual Paulista "Júlio de Mesquita Filho" Instituto de Biociências (Campus de Botucatu)..

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