IL1RAP Knockdown in LPS-Stimulated Normal Human Astrocytes Suppresses LPS-Induced Reactive Astrogliosis and Promotes Neuronal Cell Proliferation

Neurochem Res. 2023 May;48(5):1468-1479. doi: 10.1007/s11064-022-03811-w. Epub 2022 Dec 11.

Abstract

The reactivation of astrocytes plays a critical role in spinal cord injury (SCI) repairment. In this study, IL1RAP expression has been found to be upregulated in SCI mice spinal cord, SCI astrocytes, and LPS-stimulated NHAs. Genes correlated with IL1RAP were significantly enriched in cell proliferation relative pathways. In LPS-stimulated NHAs, IL1RAP overexpression promoted NHA cell proliferation, decreased PTEN protein levels, and increased the phosphorylation of Akt and mTOR. IL1RAP overexpression promoted LPS-induced NHA activation and NF-κB signaling activation. Conditioned medium from IL1RAP-overexpressing NHAs inhibited SH-SY5Y cells viability but promoted cell apoptosis. Conclusively, IL1RAP knockdown in LPS-stimulated NHAs could partially suppress LPS-induced reactive astrogliosis, therefore promoting neuronal cell proliferation.

Keywords: Astrocytes; IL1RAP; Neuronal cell; Proliferation; Reactivation; Spinal cord injury (SCI).

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Cell Proliferation / physiology
  • Gliosis / chemically induced
  • Gliosis / metabolism
  • Humans
  • Interleukin-1 Receptor Accessory Protein / metabolism
  • Lipopolysaccharides / toxicity
  • Mice
  • Neuroblastoma* / metabolism
  • Spinal Cord Injuries* / metabolism

Substances

  • Lipopolysaccharides
  • IL1RAP protein, human
  • Interleukin-1 Receptor Accessory Protein