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Sirt1 negatively regulates FcεRI-mediated mast cell activation through AMPK- and PTP1B-dependent processes

Xian Li1, Youn Ju Lee2, Fansi Jin1

  • 1College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk, 38541, Republic of Korea.

Scientific Reports
|July 27, 2017
PubMed

Insights

Sirtuin 1 (Sirt1) regulates allergic reactions by controlling mast cell activation. Activating Sirt1 with resveratrol inhibits anaphylaxis, suggesting its potential as an anti-allergy treatment.

Area of Science:

  • Immunology
  • Molecular Biology
  • Metabolism

Background:

  • Sirtuin 1 (Sirt1) is crucial for metabolism and longevity.
  • Its role in allergic reactions is emerging but not fully understood.
  • Mast cells are key players in allergic responses via FcεRI signaling.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which Sirt1 regulates mast cell activation and anaphylaxis.
  • To investigate the involvement of AMP-activated protein kinase (AMPK) and protein tyrosine phosphatase 1B (PTP1B) in Sirt1-mediated allergic responses.

Main Methods:

  • Mast cell-specific Sirt1 knockout mouse model.
  • In vitro and in vivo studies of mast cell activation.
  • Analysis of FcεRI signaling pathways, including AMPK, PTP1B, and Syk.
  • Administration of Sirt1 activator resveratrol.

Main Results:

  • Sirt1 deficiency in mast cells enhances FcεRI-stimulated activation and anaphylaxis.
  • Sirt1 negatively regulates mast cell activation via both AMPK-dependent and PTP1B-dependent pathways.
  • PTP1B attenuates AMPK signaling and enhances Syk signaling in the absence of Sirt1.
  • Resveratrol activates Sirt1, suppresses PTP1B/Syk, and inhibits anaphylaxis.

Conclusions:

  • Sirt1 acts as a negative regulator of mast cell activation and anaphylaxis.
  • The findings reveal a novel mechanism involving Sirt1, AMPK, and PTP1B in allergy.
  • Sirt1 activators like resveratrol show promise as novel anti-allergic agents.

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