Polystyrene nanoparticle exposure supports ROS-NLRP3 axis-dependent DNA-NET to promote liver inflammation

The widespread use of plastics and the rapid development of nanotechnology bring convenience to our lives while also increasing the environmental burden and increasing the risk of exposure of organisms to nanoparticles (NPs). While recent studies have revealed an association between nanoparticles and liver injury, the intrinsic mechanism of NP exposure-induced liver damage remains to be explored. Here, we found that polystyrene nanoparticle (PSNP) exposure resulted in a significant increase in local neutrophil infiltration and neutrophil extracellular trap (NET) formation in the liver. Analysis of a coculture system of PBNs and AML12 cells revealed that PSNP-induced NET formation positively correlates with the reactive oxygen species (ROS)-NLRP3 axis. Inhibition of ROS and genetic and pharmacological inhibition of NLRP3 in AML12 can both alleviate PSNP-induced NET formation. In turn, exposure of mice to deoxyribonuclease I (DNase Ⅰ)-coated PSNPs disassembled NET in vivo, neutrophil infiltration in the liver was reduced, the ROS-NLRP3 axis was inhibited, and the expression of cytokines was markedly decreased. Collectively, our work reveals a mechanism of NET formation in PSNP exposure-induced liver inflammation and highlights the possible role of DNase Ⅰ as a key enzyme in degrading NET and alleviating liver inflammation.