SET8 participates in lipopolysaccharide-mediated BV2 cell inflammation via modulation of TICAM-2 expression

Yanjun Zhao1, Xijun Yang2, Fufen Meng3

  • 1Department of Anesthesiology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, China.

Insights

SET8 modulates microglial inflammation by interacting with ATF2 to regulate TICAM-2 expression, a key factor in lipopolysaccharide-induced inflammation and sepsis-associated encephalopathy.

Area of Science:

  • Neuroscience
  • Immunology
  • Molecular Biology

Background:

  • Microglial inflammation drives sepsis-associated encephalopathy, causing neuronal apoptosis.
  • TIR domain containing adaptor molecule-2 (TICAM-2) is implicated in lipopolysaccharide (LPS)-induced microglial inflammation.
  • SET8 is a key regulator in cellular signaling pathways.

Purpose of the Study:

  • To investigate the role of SET8 in LPS-mediated microglial inflammation.
  • To determine if SET8 modulates TICAM-2 expression in this process.
  • To elucidate the molecular mechanisms underlying SET8's function.

Main Methods:

  • Utilized BV2 cell models treated with LPS.
  • Assessed expression levels of SET8, TICAM-2, and ATF2.
  • Performed co-immunoprecipitation and chromatin immunoprecipitation assays.
  • Conducted luciferase reporter assays to analyze promoter activity.

Main Results:

  • LPS upregulated TICAM-2 expression while downregulating SET8 and upregulating ATF2.
  • SET8 inhibition or ATF2 overexpression mimicked LPS effects on inflammation.
  • TICAM-2 inhibition ameliorated inflammation induced by SET8 inhibition or ATF2 overexpression.
  • SET8 interacted with ATF2, and both were enriched at the TICAM-2 promoter, with SET8 modulating its activity.

Conclusions:

  • SET8 interacts with ATF2 to regulate TICAM-2 expression, contributing to LPS-mediated microglial inflammation.
  • This pathway is crucial in the pathogenesis of sepsis-associated encephalopathy.
  • Targeting the SET8-ATF2-TICAM-2 axis may offer therapeutic strategies for neuroinflammation.