Abstract | BACKGROUND: Neuroinflammatory responses have been recognized as an important aspect in the pathogenesis of Parkinson's disease (PD). Transcriptional regulation plays a critical role in the process of inflammation. Transcription factor myocyte enhancer factor 2D (MEF2D) is identified as a central factor in transmission of extracellular signals and activation of the genetic programs in response to a wide range of stimuli in several cell types, including neurons. But its presence and function in microglia have not been reported. We therefore investigated the effect of MEF2D in activated microglia on the progress of neuroinflammation and the survival of neurons. METHODS: RESULTS: We demonstrated that MEF2D was present in microglia. Activation of microglia was associated with an increase in MEF2D level and activity in response to different stimuli in vivo and in vitro. MEF2D bound to a MEF2 consensus site in the promoter region of IL-10 gene and stimulated IL-10 transcription. Silencing MEF2D decreased the level of IL-10, increased the TNF-α mRNA, and promoted inflammation-induced cytotoxicity, consistent with the result of inhibiting IL-10 activity with an anti-IL-10 neutralizing antibody. CONCLUSIONS: Our study identifies MEF2D as a critical regulator of IL-10 gene expression that negatively controls microglia inflammation response and prevents inflammation-mediated cytotoxicity.
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Authors | Shaosong Yang, Li Gao, Fangfang Lu, Bao Wang, Fei Gao, Gang Zhu, Zhibiao Cai, Juan Lai, Qian Yang |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 12
Pg. 33
(Feb 20 2015)
ISSN: 1742-2094 [Electronic] England |
PMID | 25890150
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Aif1 protein, mouse
- Calcium-Binding Proteins
- Lipopolysaccharides
- MEF2 Transcription Factors
- Microfilament Proteins
- RNA, Messenger
- Interleukin-10
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- Tyrosine 3-Monooxygenase
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Topics |
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(pharmacology)
- Animals
- Animals, Newborn
- Apoptosis
(drug effects, physiology)
- Brain
(cytology)
- Calcium-Binding Proteins
(metabolism)
- Cells, Cultured
- Chromatin Immunoprecipitation
- Electrophoretic Mobility Shift Assay
- Interleukin-10
(genetics, metabolism)
- Lipopolysaccharides
(toxicity)
- MEF2 Transcription Factors
(genetics, metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- Microfilament Proteins
(metabolism)
- Microglia
(drug effects, metabolism)
- RNA, Messenger
(metabolism)
- Time Factors
- Tyrosine 3-Monooxygenase
(metabolism)
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