Promotion of 14-3-3ζ/Heme Oxygenase-1 Axis on Endotoxin-Induced Uveitis and Microglia Ferroptosis in Mice

Ocul Immunol Inflamm. 2024 Nov;32(9):2114-2120. doi: 10.1080/09273948.2024.2328784. Epub 2024 Apr 12.

Abstract

Purpose: Uveitis is a common, sight-threatening inflammatory ocular disease and is the main cause of blindness, which is caused by autoimmune response, infection, and injury. The contribution of 14-3-3ζ in uveitis remains obscure. This study aims to investigate the role of 14-3-3ζ in regulating ferroptosis in retinal inflammation and its contribution to uveitis.

Methods: A lipopolysaccharide (LPS)-induced uveitis mouse model and BV-2 cell line were used to examine the effect of LPS stimulation on the expression of 14-3-3ζ and ferroptosis in microglia. The expression of heme oxygenase-1 (HO-1) was also analyzed to understand its role in promoting microglial ferroptosis.

Results: We found that LPS stimulation increased the expression of 14-3-3ζ and promoted ferroptosis in microglia. Additionally, 14-3-3ζ was found to promote microglial ferroptosis by stabilizing the expression of HO-1. These findings suggest that the 14-3-3ζ/HO-1 axis plays a crucial role in promoting microglial ferroptosis in retinal inflammation.

Conclusion: The study provides valuable insights into the mechanisms underlying uveitis and highlights the potential of the 14-3-3ζ/HO-1 axis as a therapeutic target for the disease. Further research in this area could lead to the development of preventive and therapeutic strategies for uveitis.

Keywords: 14-3-3ζ; ferroptosis; heme oxygenase-1; microglia; uveitis.

MeSH terms

  • 14-3-3 Proteins* / genetics
  • 14-3-3 Proteins* / metabolism
  • Animals
  • Blotting, Western
  • Disease Models, Animal*
  • Ferroptosis* / physiology
  • Heme Oxygenase-1* / genetics
  • Heme Oxygenase-1* / metabolism
  • Lipopolysaccharides*
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL*
  • Microglia* / metabolism
  • Uveitis* / chemically induced
  • Uveitis* / metabolism

Substances

  • Heme Oxygenase-1
  • 14-3-3 Proteins
  • Lipopolysaccharides
  • Hmox1 protein, mouse
  • Membrane Proteins