Immunoglobulins reduced oxidative stress in human microglial cells induced by high dose of acetoacetate

Hongxin Chen, Nizar Souayah

Research output: Contribution to journalArticlepeer-review

Abstract

Diabetic ketoacidosis (DKA) has been associated with cognitive impairment and structural alterations in the brain. There is increased evidence supporting the role of neuroinflammation in causing these alterations. In the present study, using human microglial cell line (CHME-5), we aimed to investigate the effect of immunoglobulins (IG) on survival, activation, reactive oxygen species (ROS) and cytokine production of microglia exposed to ketone bodies. We demonstrated that high and low dose of ketone bodies induced a significant increase in ROS within 1 h after exposure to CHME-5 cells with upregulation in mitochondrial superoxide level 5 min after exposure suggestive of early and selective impairment of mitochondrial function. A significant and delayed increase of apoptosis of CHME-5 cells was observed 4 days after ketone bodies exposure. Cytokine expression reached a peak within 1 h and persisted for 3 days after exposure to ketone bodies. IG significantly reduced ROS and transiently suppressed cytokine expression of CHME-5 cells after exposure to ketone bodies. However, no effect of IG on apoptosis was observed. Overall, these results supported that ketone bodies induced microglia activation with early and selective impairment of mitochondrial function, increased cytokines expression and delayed increase in apoptosis. IG suppressed microglia activation and transiently inhibited cytokines expression without affecting apoptosis. These results warrant further experimental work on the role of microglia and potential benefit of IG in brain structural changes induced by DKA.

Original languageEnglish (US)
Article number147054
JournalBrain research
Volume1748
DOIs
StatePublished - Dec 1 2020

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Keywords

  • Apoptosis
  • Cell death
  • Cytokines expression
  • Diabetic ketoacidosis
  • Intravenous immunoglobulin (IVIG)
  • Ketone bodies
  • Microglia

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