Involvement of mast cells in the protective effect of vitamin D on experimental autoimmune encephalomyelitis

• Grant number: 14/00239-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2014
• Effective date (End): April 30, 2017
• Field of knowledge: Biological Sciences - Immunology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Alexandrina Sartori
• Grantee: Karen Henriette Pinke
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Multiple Sclerosis (MS) is among the neurological diseases with higher mundial incidence (30 cases/100,000 inhabitants). MS cause demyelination areas and axonal damage in the Central Nervous System (CNS) due to autoimmune response developed by Th1, Th17 and Tc lymphocytes. Experimental autoimmune encephalomyelitis (EAE) it is the main model to study. The involvement of mast cells in MS/EAE is not fully understood. Theoretically these cells act as mediators of the inflammatory process or as regulators of the immune response. Mast cells express the vitamin D receptor (VDR), implicated as an immunomodulator in autoimmune diseases. Considering the inflammatory and immunomodulatory potential of the mast cells, their location in the CNS and the possible action of vitamin D on these cells, the aim of this work is to evaluate whether the protective effect of vitamin D in EAE is associated with modulation of the mast cells activity. For this, C57BL/6 mice immunized with MOG will be treated with vitamin D, ketotifen or 48/80 compound. The effectiveness of treatments will be analyzed by determinations of the body weight, the clinical score, the presence and activation of mast cells in the CNS by immunohistochemistry and through the release of tryptase and chymase in tissue. The effect of vitamin D also be assessed in vitro by degranulation (² - hexosaminidase assay) and release of histamine (ELISA - IBL -America), tryptase (mast cell degranulation kit from Millipore ®) and the production of TNF- ±, IL -10 (Mouse OptEIA ELISA Set , BD Biosciences), IL- 6, IL -12, IL-21 , IL -23 and TGF- ² (mouse ELISA Ready- SET- Go ® - eBioscience). Besides the surface expression of the MHC I, MHC II, CD40L, OX40L and VDR (flow cytometry) on mast cells differentiated from bone marrow cells of the mice. Statistical tests will be applied according to the presence or absence of normality in the ratings (p <0,05). (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PINKE, KAREN HENRIETTE; GONCALVES ZORZELLA-PEZAVENTO, SOFIA FERNANDA; LARA, VANESSA SOARES; SARTORI, ALEXANDRINA. Should mast cells be considered therapeutic targets in multiple sclerosis?. NEURAL REGENERATION RESEARCH, v. 15, n. 11, p. 1995-2007, NOV 2020. (15/03965-2, 14/00239-6)

PINKE, KAREN HENRIETTE; ZORZELLA-PEZAVENTO, SOFIA FERNANDA GONCALVES; DE CAMPOS FRAGA-SILVA, THAIS FERNANDA; MIMURA, LUIZA AYUMI NISHIYAMA; DE OLIVEIRA, LARISSA RAGOZO CARDOSO; ISHIKAWA, LARISSA LUMI WATANABE; FERNANDES, ANA ANGELICA HENRIQUE; LARA, VANESSA SOARES; SARTORI, ALEXANDRINA. Calming Down Mast Cells with Ketotifen: A Potential Strategy for Multiple Sclerosis Therapy?. NEUROTHERAPEUTICS, v. 17, n. 1, SI, p. 218-234, JAN 2020. (14/00239-6)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

PINKE, Karen Henriette. Effect of mast cell stabilization on experimental autoimmune encephalomyelitis development. 2017. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu Botucatu.