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Dimethyl fumarate downregulates the immune response through the HCA2/GPR109A pathway: Implications for the treatment of multiple sclerosis.
von Glehn, Felipe; Dias-Carneiro, Rafael P C; Moraes, Adriel S; Farias, Alessandro S; Silva, Veronica A P G; Oliveira, Francisco T M; Silva, Carlos Eduardo B G; de Carvalho, Fabricio; Rahal, Elaine; Baecher-Allan, Clare; Santos, Leonilda M B.
Afiliação
  • von Glehn F; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, USA; Neuroimmunology Unit, Department of Genetics, Evolution and Bioagents, Institute of Biology; University of Campinas, Campinas, Brazil. Electronic address: felipeglehn@gmail.com.
  • Dias-Carneiro RPC; Neuroimmunology Unit, Department of Genetics, Evolution and Bioagents, Institute of Biology; University of Campinas, Campinas, Brazil; CATEM- Center for Multiple Sclerosis Care, Santa Casa de São Paulo, São Paulo, Brazil.. Electronic address: r.paterno@me.com.
  • Moraes AS; Neuroimmunology Unit, Department of Genetics, Evolution and Bioagents, Institute of Biology; University of Campinas, Campinas, Brazil. Electronic address: moraesadr@yahoo.com.br.
  • Farias AS; Neuroimmunology Unit, Department of Genetics, Evolution and Bioagents, Institute of Biology; University of Campinas, Campinas, Brazil; National Institute for Science and Technology - Neuroimmunomodulation (INCT-NIM), CNPq, Brazil. Electronic address: farias.as@gmail.com.
  • Silva VAPG; Neuroimmunology Unit, Department of Genetics, Evolution and Bioagents, Institute of Biology; University of Campinas, Campinas, Brazil. Electronic address: veronicaalmeida1@yahoo.com.br.
  • Oliveira FTM; Neuroimmunology Unit, Department of Genetics, Evolution and Bioagents, Institute of Biology; University of Campinas, Campinas, Brazil; CATEM- Center for Multiple Sclerosis Care, Santa Casa de São Paulo, São Paulo, Brazil.. Electronic address: towmaz@gmail.com.
  • Silva CEBG; Biogen, São Paulo, SP, Brazil. Electronic address: carlos.dasilva@biogen.com.
  • de Carvalho F; Biogen, São Paulo, SP, Brazil. Electronic address: fabricio.carvalho.phd@gmail.com.
  • Rahal E; Biogen, São Paulo, SP, Brazil. Electronic address: elaine.rahal@biogen.com.
  • Baecher-Allan C; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, USA. Electronic address: callan@rics.bwh.harvard.edu.
  • Santos LMB; Neuroimmunology Unit, Department of Genetics, Evolution and Bioagents, Institute of Biology; University of Campinas, Campinas, Brazil; National Institute for Science and Technology - Neuroimmunomodulation (INCT-NIM), CNPq, Brazil. Electronic address: leonilda@unicamp.br.
Mult Scler Relat Disord ; 23: 46-50, 2018 Jul.
Article em En | MEDLINE | ID: mdl-29763776
ABSTRACT

BACKGROUND:

The mechanisms of action of dimethyl fumarate (DMF), and its metabolite, monomethyl fumarate (MMF), for the treatment of multiple sclerosis are not completely elucidated.

OBJECTIVES:

To discuss the role of DMF/MMF-induced hydroxycarboxylic acid receptor 2 (HCA2/GPR109A) pathway activation in the immune response and treatment of MS.

METHODS:

A narrative (traditional) review of the current literature.

RESULTS:

Studies have shown that binding of DMF/MMF to HCA2 on dendritic cells inhibits the production of pro-inflammatory cytokines in vitro and in MS murine models. Evidence suggests that activation of HCA2 expressed in immune cells and gut epithelial cells by DMF/MMF, may induce anti-inflammatory responses in the intestinal mucosa.

CONCLUSION:

Although the DMF/MMF mechanism of action remains unclear, evidence suggests that the activation of HCA2/GPR109A pathway downregulates the immune response and may activate anti-inflammatory response in the intestinal mucosa, possibly leading to reduction in CNS tissue damage in MS patients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Nicotínicos / Receptores Acoplados a Proteínas G / Fumarato de Dimetilo / Imunossupressores / Esclerose Múltipla Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Nicotínicos / Receptores Acoplados a Proteínas G / Fumarato de Dimetilo / Imunossupressores / Esclerose Múltipla Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article