Research articleKrüppel-like factor 4 regulates amyloid-β (Aβ)-induced neuroinflammation in Alzheimer's disease

- Oligomeric Aβ42 increases the Klf4 expression in microglial BV2 cells.
- Gene and protein expressions of Klf4 are increased in brain microglia of AD mice.
- p53 mediates Aβ42-induced expression of Klf4.
- Silence of Klf4 restores Aβ42-induced neuroinflammation.
- Overexpression of Klf4 exacerbates Aβ42-induced neuroinflammation.

Alzheimer's disease (AD), one of the most common neurodegenerative diseases, is characterized by extracellular deposition of amyloid-β (Aβ) peptide, and neuro-inflammatory processes mediated by microglial activation are known to play a pivotal role in AD. However, the expression pattern and function of Krüppel-like factor (KLF) 4 in AD remain unknown. In this study, KLF4 was found to be increased at both the gene and protein levels in response to incubation with oligomeric Aβ42 in a dose-dependent manner in BV2 microglial cells. An in vivo study also displayed that expression of KLF4 in the brains of J20 transgenic AD model mice was increased due to accumulation of Aβ. Mechanistically, activation of p53 resulting from an increase in phosphorylation at ser15 was verified as the mediator of the oligomeric Aβ42-induced expression of KLF4. Subsequent experiments have demonstrated that KLF4 silencing in BV2 cells attenuates oligomeric Aβ42-induced neuroinflammation by ameliorating the release of proinflammatory cytokines, such as tumor necrosis factor-a (TNF-α), interleukin (IL)-1β, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). In addition, overexpression of KLF4 promoted oligomeric Aβ42-induced neuroinflammation by exacerbating the release of pro-inflammatory factors. These results suggest a KLF4 plays a potential role in oligomeric Aβ42-induced neurotoxicity and the pathogenesis of AD.