Neutrophil extracellular traps prime the ZBP1-cGAS sensor complex, triggering necroptosis and inflammatory injury in acute pancreatitis - PubMed
4 days ago
- #Necroptosis
- #Mitochondrial DNA
- #Acute Pancreatitis
- Neutrophil extracellular traps (NETs) levels correlate with the severity of severe acute pancreatitis (SAP).
- NETs activate the ZBP1-cGAS complex via mitochondrial DNA (mtDNA), triggering necroptosis and inflammatory pathways.
- NETs induce mitochondrial damage in acinar cells, leading to cytosolic accumulation of mtDNA.
- ZBP1 stabilizes Z-form mtDNA and enhances cGAS recognition, promoting necroptosis and inflammation.
- Cyclosporine A inhibits mtDNA release, suppressing NETs-induced ZBP1-cGAS complex formation and reducing pancreatic injury.
- The mtDNA-ZBP1-cGAS axis is identified as a key mechanism by which NETs exacerbate pancreatic inflammation.