IDH2 Deficiency in Microglia Decreases the Pro-inflammatory Response via the ERK and NF-κB Pathways
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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.
KEY WORDSIsocitrate dehydrogenase 2 Pro-inflammatory mediator Lipopolysaccharide Microglia ERK NF-κB
This research was supported by grants from the National Research Foundation of Korea, funded by the government of Republic of Korea (NRF-2015R1A4A1042271, NRF-2017R1A2B4008176, NRF-2017R1A5A2015391).
Compliance with Ethical Standards
All animal experiments performed in accordance with the guidelines of the Animal Care Committee of Kyungpook National University.
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