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

• DOI: 10.1186/s10020-018-0006-9
• Publication Date: 2018-03-14T13:47:39Z
• Authors: Sujun Li; Fang Liang; Kevin Kwan; Yiting Tang; Xiangyu Wang; Youzhou Tang; Jianhua Li; Huan Yang; Sangeeta S. Chavan; Haichao Wang; Ulf Andersson; Ben Lu; Kevin J. Tracey
• Keywords: HMGB1; Nigericin; AIM2; Mitochondrial ROS; Pyroptosis

The NLRP3 inflammasome, a cytosolic complex that mediates the maturation of IL-1β and IL-18 as well release high mobility group box 1 (HMGB1), contributes to lethality endotoxic shock. Ethyl pyruvate (EP) was previously shown inhibit HMGB1 promote survival during endotoxemia experimental sepsis. However, underlying protective mechanism remains elusive. EP dose-dependently inhibited ATP-, nigericin-, alum-, silica-induced caspase-1 activation in mouse macrophages. failed DNA transfection- or Salmonella Typhimurium-induced release. Mechanistically, significantly attenuated mitochondrial damage cytoplasmic translocation DNA, known ligand, without influencing potassium efflux, lysosomal rupture production reactive oxygen species (mtROS). acts novel inflammasome inhibitor preserves integrity mitochondria inflammation.