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Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia

Dimethylfumarate (DMF) has been approved the for treatment of relapsing-remitting multiple sclerosis. The mode of action of DMF and its assumed active primary metabolite monomethylfumarate (MMF) is still not fully understood, notably for brain resident cells. Therefore we investigated potential dire...

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Autores principales: Kronenberg, Jessica, Pars, Kaweh, Brieskorn, Marina, Prajeeth, Chittappen K., Heckers, Sandra, Schwenkenbecher, Philipp, Skripuletz, Thomas, Pul, Refik, Pavlou, Andreas, Stangel, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358967/
https://www.ncbi.nlm.nih.gov/pubmed/30650518
http://dx.doi.org/10.3390/ijms20020325
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author Kronenberg, Jessica
Pars, Kaweh
Brieskorn, Marina
Prajeeth, Chittappen K.
Heckers, Sandra
Schwenkenbecher, Philipp
Skripuletz, Thomas
Pul, Refik
Pavlou, Andreas
Stangel, Martin
author_facet Kronenberg, Jessica
Pars, Kaweh
Brieskorn, Marina
Prajeeth, Chittappen K.
Heckers, Sandra
Schwenkenbecher, Philipp
Skripuletz, Thomas
Pul, Refik
Pavlou, Andreas
Stangel, Martin
author_sort Kronenberg, Jessica
collection PubMed
description Dimethylfumarate (DMF) has been approved the for treatment of relapsing-remitting multiple sclerosis. The mode of action of DMF and its assumed active primary metabolite monomethylfumarate (MMF) is still not fully understood, notably for brain resident cells. Therefore we investigated potential direct effects of DMF and MMF on microglia and indirect effects on oligodendrocytes. Primary rat microglia were differentiated into M1-like, M2-like and M0 phenotypes and treated in vitro with DMF or MMF. The gene expression of pro-inflammatory and anti-inflammatory factors such as growth factors (IGF-1), interleukins (IL-10, IL-1β), chemokines (CCl3, CXCL-10) as well as cytokines (TGF-1β, TNFα), iNOS, and the mannose receptor (MRC1) was examined by determining their transcription level with qPCR, and on the protein level by ELISA and FACS analysis. Furthermore, microglia function was determined by phagocytosis assays and indirect effects on oligodendroglial proliferation and differentiation. DMF treatment of M0 and M1-like polarized microglia demonstrated an upregulation of gene expression for IGF-1 and MRC1, but not on the protein level. While the phagocytic activity remained unchanged, DMF and MMF treated microglia supernatants led to an enhanced proliferation of oligodendrocyte precursor cells (OPC). These results suggest that DMF has anti-inflammatory effects on microglia which may result in enhanced proliferation of OPC.
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spelling pubmed-63589672019-02-06 Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia Kronenberg, Jessica Pars, Kaweh Brieskorn, Marina Prajeeth, Chittappen K. Heckers, Sandra Schwenkenbecher, Philipp Skripuletz, Thomas Pul, Refik Pavlou, Andreas Stangel, Martin Int J Mol Sci Article Dimethylfumarate (DMF) has been approved the for treatment of relapsing-remitting multiple sclerosis. The mode of action of DMF and its assumed active primary metabolite monomethylfumarate (MMF) is still not fully understood, notably for brain resident cells. Therefore we investigated potential direct effects of DMF and MMF on microglia and indirect effects on oligodendrocytes. Primary rat microglia were differentiated into M1-like, M2-like and M0 phenotypes and treated in vitro with DMF or MMF. The gene expression of pro-inflammatory and anti-inflammatory factors such as growth factors (IGF-1), interleukins (IL-10, IL-1β), chemokines (CCl3, CXCL-10) as well as cytokines (TGF-1β, TNFα), iNOS, and the mannose receptor (MRC1) was examined by determining their transcription level with qPCR, and on the protein level by ELISA and FACS analysis. Furthermore, microglia function was determined by phagocytosis assays and indirect effects on oligodendroglial proliferation and differentiation. DMF treatment of M0 and M1-like polarized microglia demonstrated an upregulation of gene expression for IGF-1 and MRC1, but not on the protein level. While the phagocytic activity remained unchanged, DMF and MMF treated microglia supernatants led to an enhanced proliferation of oligodendrocyte precursor cells (OPC). These results suggest that DMF has anti-inflammatory effects on microglia which may result in enhanced proliferation of OPC. MDPI 2019-01-15 /pmc/articles/PMC6358967/ /pubmed/30650518 http://dx.doi.org/10.3390/ijms20020325 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kronenberg, Jessica
Pars, Kaweh
Brieskorn, Marina
Prajeeth, Chittappen K.
Heckers, Sandra
Schwenkenbecher, Philipp
Skripuletz, Thomas
Pul, Refik
Pavlou, Andreas
Stangel, Martin
Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia
title Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia
title_full Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia
title_fullStr Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia
title_full_unstemmed Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia
title_short Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia
title_sort fumaric acids directly influence gene expression of neuroprotective factors in rodent microglia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358967/
https://www.ncbi.nlm.nih.gov/pubmed/30650518
http://dx.doi.org/10.3390/ijms20020325
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