查看文章

Acetaminophen (APAP) overdose is a leading cause of acute liver failure worldwide, in which mitochondrial DNA (mtDNA) released by damaged hepatocytes activates neutrophils through binding of Toll‐like receptor 9 (TLR9), further aggravating liver injury. Here, we demonstrated that mtDNA/TLR9 also activates a negative feedback pathway through induction of microRNA‐223 (miR‐223) to limit neutrophil overactivation and liver injury. After injection of APAP in mice, levels of miR‐223, the most abundant miRNAs in neutrophils, were highly elevated in neutrophils. Disruption of the miR‐223 gene exacerbated APAP‐induced hepatic neutrophil infiltration, oxidative stress, and injury and enhanced TLR9 ligand‐mediated activation of proinflammatory mediators in neutrophils. An additional deletion of the intercellular adhesion molecule 1 (ICAM‐1) gene ameliorated APAP‐induced neutrophil infiltration and liver …