CD97/ADGRE5 Inhibits LPS Induced NF-κB Activation through PPAR-γ Upregulation in Macrophages

Shuai Wang1, Zewei Sun1, Wenting Zhao1

  • 1Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.

Insights

CD97 protein suppresses lipopolysaccharide (LPS)-induced NF-κB activation and TNF-α secretion in macrophages, partly by upregulating the anti-inflammatory transcription factor PPAR-γ.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • CD97/ADGRE5, an EGF-TM7 receptor family member, is expressed on leukocytes and influences inflammatory responses.
  • Its role in lipopolysaccharide (LPS)-induced nuclear factor-kappa B (NF-κB) activation in macrophages remains unexplored.

Purpose of the Study:

  • To investigate the role of CD97 in LPS-induced NF-κB activation and inflammatory factor production in macrophages.
  • To elucidate the involvement of PPAR-γ in CD97-mediated regulation of NF-κB signaling.

Main Methods:

  • Assessed CD97 expression in LPS-treated human primary macrophages.
  • Manipulated CD97 levels (knockdown/overexpression) and analyzed NF-κB and TNF-α.
  • Utilized immunofluorescence staining to examine p65 and PPAR-γ expression.
  • Employed CD97 knockout THP-1 cells to confirm findings.

Main Results:

  • CD97 overexpression inhibited LPS-induced p65 nuclear translocation and TNF-α secretion.
  • CD97 manipulation affected PPAR-γ expression, suggesting its involvement in the pathway.
  • CD97 knockout cells showed decreased LPS-induced NF-κB activation.
  • CD97 was found to promote PPAR-γ expression.

Conclusions:

  • CD97 negatively regulates LPS-induced NF-κB activation and TNF-α secretion in macrophages.
  • This suppression is partly mediated by the upregulation of PPAR-γ.
  • CD97 plays a crucial role in modulating inflammatory responses in macrophages.