Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia.
Animals
Cell Differentiation
/ drug effects
Cell Proliferation
/ drug effects
Dimethyl Fumarate
/ pharmacology
Fumarates
/ pharmacology
Gene Expression Regulation
/ drug effects
Insulin-Like Growth Factor I
/ metabolism
Maleates
/ pharmacology
Microglia
/ drug effects
Neuroprotective Agents
/ metabolism
Oligodendroglia
/ cytology
Phagocytosis
/ drug effects
Rats, Sprague-Dawley
Stem Cells
/ cytology
IGF-1
dimethylfumarate
microglia
monomethylfumarate
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
15 Jan 2019
15 Jan 2019
Historique:
received:
22
12
2018
revised:
10
01
2019
accepted:
11
01
2019
entrez:
18
1
2019
pubmed:
18
1
2019
medline:
30
4
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30650518
pii: ijms20020325
doi: 10.3390/ijms20020325
pmc: PMC6358967
pii:
doi:
Substances chimiques
Fumarates
0
Maleates
0
Neuroprotective Agents
0
citraconic acid
0RQ6CXO9KD
Insulin-Like Growth Factor I
67763-96-6
fumaric acid
88XHZ13131
Dimethyl Fumarate
FO2303MNI2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Biogen Germany
ID : --
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