Iron accumulation induces oxidative stress, while depressing inflammatory polarization in human iPSC-derived microglia.

ABSTRACT: Iron accumulation in microglia has been observed in Alzheimer's disease and other neurodegenerative disorders and is thought to contribute to disease progression through various mechanisms, including neuroinflammation. To study this interaction, we treated human induced pluripotent stem cell-derived microglia (iPSC-MG) with iron, in combination with inflammatory stimuli such as interferon gamma (IFN-γ) and amyloid β. Both IFN-γ and iron treatment increased labile iron levels, but only iron treatment led to a consistent increase of ferritin levels, reflecting long-term iron storage. Therefore, in iPSC-MG, ferritin appeared to be regulated by iron revels rather than inflammation. Further investigation showed that while IFN-γ induced pro-inflammatory activation, iron treatment dampened both c

SUBMITTER: Kenkhuis B 

PROVIDER: S-EPMC9213827 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature