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Updated: Feb 6, 2026

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

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Identification of ethyl pyruvate as a NLRP3 inflammasome inhibitor that preserves mitochondrial integrity

Sujun Li1, Fang Liang1, Kevin Kwan2

  • 1Department of Hematology and Key Laboratory of non-resolving inflammation and cancer of Human Province, The 3rd Xiangya Hospital, Central South University, Changsha, Hunan province, 410000, People's Republic of China.

Molecular Medicine (Cambridge, Mass.)
|August 24, 2018
PubMed
Abstract

Insights

Ethyl pyruvate (EP) inhibits the NLRP3 inflammasome, a key driver of inflammatory diseases like endotoxic shock. This compound protects mitochondria, offering a novel therapeutic strategy for inflammation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • The NLRP3 inflammasome is crucial for maturation of IL-1β and IL-18, and HMGB1 release, contributing to endotoxic shock.
  • Ethyl pyruvate (EP) has shown promise in improving survival during endotoxemia and sepsis by inhibiting HMGB1 release, but its mechanism was unclear.

Purpose of the Study:

  • To elucidate the protective mechanism of Ethyl pyruvate (EP) against NLRP3 inflammasome activation and its role in inflammation.

Main Methods:

  • Investigated EP's effect on caspase-1 activation and HMGB1 release in mouse macrophages stimulated with various NLRP3 activators.
  • Assessed EP's impact on mitochondrial damage, mitochondrial DNA translocation, potassium efflux, lysosomal rupture, and mitochondrial reactive oxygen species (mtROS) production.

Main Results:

  • EP dose-dependently inhibited caspase-1 activation and HMGB1 release induced by ATP, nigericin, alum, and silica.
  • EP did not inhibit caspase-1 activation or HMGB1 release induced by DNA transfection or Salmonella Typhimurium.
  • EP attenuated mitochondrial damage and cytoplasmic translocation of mitochondrial DNA, a NLRP3 ligand, without affecting potassium efflux, lysosomal rupture, or mtROS.

Conclusions:

  • Ethyl pyruvate (EP) functions as a novel inhibitor of the NLRP3 inflammasome.
  • EP preserves mitochondrial integrity, offering a new therapeutic avenue for inflammatory conditions by targeting NLRP3 inflammasome activation.
Keywords:
Ethyl pyruvateHMGB1Interleukin-1betaMitochondrial damageThe NLRP3 inflammasomes

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