Dimethyl fumarate downregulates the immune response through the HCA 2 /GPR109A pathway: Implications for the treatment of multiple sclerosis.

Autor: 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.
Jazyk: angličtina
Zdroj: Multiple sclerosis and related disorders [Mult Scler Relat Disord] 2018 Jul; Vol. 23, pp. 46-50. Date of Electronic Publication: 2018 Apr 25.
DOI: 10.1016/j.msard.2018.04.016
Abstrakt: 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 (HCA 2 /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 HCA 2 on dendritic cells inhibits the production of pro-inflammatory cytokines in vitro and in MS murine models. Evidence suggests that activation of HCA 2 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 HCA 2 /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.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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