The oncometabolite R-2-hydroxyglutarate inhibits microglial activation via the FTO/NF-κB pathway.

ABSTRACT:

Introduction

Mutations in isocitrate dehydrogenase 1 (mIDH1) generate the oncometabolite (R)-2-hydroxyglutarate (R-2HG), which promotes tumorigenesis by inhibiting α-ketoglutarate-dependent enzymes and altering the epigenetic landscape. Microglia, the resident brain macrophages, are a key immune population in gliomas. While R-2HG is known to impair CD8+ T-cell function, its specific impact on microglial activation remains unknown. This study aimed to investigate the effect of R-2HG on microglial inflammatory responses.

Methods

The murine microglial BV2 cell line was stimulated with glioma-conditioned medium (CM) in the presence or absence of R-2HG. Cytokine production was analyzed, with a specific focus on IL-6. Mechanistic studies involved assessing the phosphorylation and

SUBMITTER: Wang L 

PROVIDER: S-EPMC12683333 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature