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Notch signaling regulates expression of Mcl-1 and apoptosis in PPD-treated macrophages

Tanapat Palaga1, Siriluk Ratanabunyong, Thitiporn Pattarakankul

  • 1Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand. tanapat.p@chula.ac.th

Cellular & Molecular Immunology
|July 23, 2013
PubMed

Insights

Tuberculin purified protein derivative (PPD) stimulates Notch1 signaling in macrophages, which upregulates the anti-apoptotic gene mcl-1. This Notch1-Mcl-1 pathway prevents macrophage apoptosis during infection, aiding pathogen survival.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Macrophages are crucial immune cells targeted by pathogens.
  • Macrophage apoptosis is a key host defense mechanism.
  • The role of Notch signaling in macrophage apoptosis is not fully understood.

Purpose of the Study:

  • To investigate the role of Notch signaling in regulating macrophage apoptosis induced by tuberculin purified protein derivative (PPD).

Main Methods:

  • Murine bone marrow-derived macrophages (BMMs) and RAW264.7 cell line were used.
  • Cells were treated with PPD or Mycobacterium bovis Bacillus Calmette-Guérin (BCG).
  • Notch signaling was inhibited using a gamma secretase inhibitor (GSI) and by Notch1 silencing.

Main Results:

  • PPD treatment upregulated Notch1 and the anti-apoptotic gene mcl-1 in macrophages.
  • Inhibition of Notch signaling with GSI or Notch1 silencing decreased Mcl-1 levels and increased apoptosis.
  • Notch1 directly binds to the mcl-1 promoter, regulating its expression.

Conclusions:

  • Notch1 signaling inhibits PPD-induced macrophage apoptosis by directly controlling mcl-1 expression.
  • This pathway may be exploited by pathogens to evade host immune responses.
  • Targeting Notch1-Mcl-1 interaction could be a therapeutic strategy.

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