Inhibitory effect of IL-27 on the overactivation of microglia

Neuroinflammation mediated by microglia is essential for the occurrence and development of Alzheimer’s disease (AD). Through the analysis of the GEO database, it was found that IL-27 expression decreased in both the cerebral cortex and hippocampus of AD patients. In this study, the AD cell model of BV-2 cells injured by Aβ_1-42, the inflammatory cell model of BV-2 cells damaged by LPS, and the inflammatory animal model were established and the effects of IL-27 after its administration in the above models in regulating microglial phenotype and neuroinflammation were evaluated. In the animal models, the number of Iba1+ microglia in the hippocampus was detected by immunohistochemistry, the expression of pro-inflammatory factors such as TNF-α, IL-1β and IL-6 was detected by qPCR, ELISA and Western blot, and the expression of M1/M2 phenotypic markers in microglia was detected by qPCR. To further explore the action mechanism of IL-27, Western blot was used to detect the expression levels of NF-κB, p-NF-κB, IκBα and p-IκBα in microglia after administration of IL-27 and Aβ_1-42. The results showed that IL-27 alleviated the abnormal activation of microglia induced by lipopolysaccharide (LPS), decreased the expression of pro-inflammatory factors such as TNF- α, IL-1β and IL-6, transformed microglia induced by LPS or Aβ_1-42 from neurotoxic M1 to neuroprotective M2, and improved the abnormal phosphorylation of NF-κB and IκBα induced by Aβ_1-42. The research suggested that IL-27 can regulate the M1/M2 polarization of microglia induced by Aβ_1-42 or LPS, and alleviate neuroinflammation.