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Inflammation. 2018 Oct;41(5):1965-1973. doi: 10.1007/s10753-018-0840-5.

IDH2 Deficiency in Microglia Decreases the Pro-inflammatory Response via the ERK and NF-κB Pathways.

Chae U1,2, Kim HS1,2, Kim KM1,2, Lee H1,2,3, Lee HS1,2, Park JW1,2, Lee DS4,5.

Author information

1
School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
2
College of Natural Sciences, Kyungpook National University, Daegu, 41566, Republic of Korea.
3
New Drug Development Center, DGMIF, Daegu, Republic of Korea.
4
School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea. lee1@knu.ac.kr.
5
College of Natural Sciences, Kyungpook National University, Daegu, 41566, Republic of Korea. lee1@knu.ac.kr.

Abstract

In various neuronal diseases, the activation of microglia contributes to the production of excessive neurotoxic factors, such as pro-inflammatory mediators. In particular, the overproduction of pro-inflammatory cytokines and nitric oxide (NO) has critical effects on the development of neurodegenerative diseases and gliomas in the brain. Recent studies have suggested that isocitrate dehydrogenase 2 (IDH2) plays a key role in inducing gliomas and neurodegeneration. IDH2 dysfunction has been linked to various cancers and neurodegenerative diseases associated with uncontrolled inflammatory responses, such as the excessive generation of pro-inflammatory cytokines. In this study, we demonstrate that IDH2 contributes to the regulation of pro-inflammatory mediators in microglia. The downregulation of IDH2 decreased the lipopolysaccharide (LPS)-induced pro-inflammatory response in BV-2 and primary microglial cells. Furthermore, IDH2 deficiency downregulated pro-inflammatory mediators via modulation of the ERK and NF-κB pathways. These results indicate that IDH2 is a potential target for the regulation of pro-inflammatory responses in LPS-activated microglial cells. Our findings also provide a basis for the development of new therapies for pro-inflammatory responses in dysfunction-associated neuronal diseases.

KEYWORDS:

ERK; Isocitrate dehydrogenase 2; Lipopolysaccharide; Microglia; NF-κB; Pro-inflammatory mediator

PMID:
29987482
DOI:
10.1007/s10753-018-0840-5
[Indexed for MEDLINE]

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