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ATP Mediates Pyroptosis in the Intestinal Mucosal System During Colitis.

Sihyun Jeong1, Soyeong Park1, Doyeon Lee1

  • 1Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, Republic of Korea.

Journal of Cellular Physiology
|July 21, 2025
PubMed
Summary

Extracellular ATP acts as a damage-associated molecular pattern (DAMP) to trigger pyroptosis in intestinal epithelial cells during colitis. Elevated ATP levels promote inflammation and cell death, exacerbating the condition.

Keywords:
ATPcolitisinflammationintestinepyroptosis

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Area of Science:

  • Immunology
  • Gastroenterology
  • Cell Biology

Background:

  • Damage-associated molecular patterns (DAMPs) are released by stressed cells, promoting inflammation.
  • Extracellular ATP is a DAMP primarily studied in monocytes, but its role in the gut is less understood.

Purpose of the Study:

  • To investigate extracellular ATP's role as a DAMP in inducing pyroptosis within the intestinal mucosal system.
  • To analyze ATP levels and pyroptosis mediators in a mouse model of colitis.

Main Methods:

  • Induced colitis in mice using dextran sodium sulfate.
  • Measured ATP levels and pyroptosis-related protein expression in colonic tissues and serum.
  • Treated colonic epithelial cells with ATP in vitro to assess cell death and pyroptosis.

Main Results:

  • Colitis mice showed increased ATP levels in the colon and serum.
  • Pyroptosis mediators were significantly upregulated in colons of colitis mice.
  • In vitro ATP treatment induced cell death, mitochondrial dysfunction, and pyroptosis in colonic epithelial cells, but not apoptosis.

Conclusions:

  • Extracellular ATP acts as a DAMP to induce pyroptosis in intestinal epithelial cells during colitis.
  • Elevated ATP levels contribute to a self-propagating cycle of pyroptosis, worsening intestinal inflammation.
  • This study expands the understanding of ATP-mediated pyroptosis to the intestinal context.