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 dis-assembled 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 for-mation 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.

Automated summary

The use of plastics and nanotechnology has brought convenience to our lives, but it also increases the environmental burden and the risk of exposure to nanoparticles. This study reveals that exposure to polystyrene nanoparticles (PSNPs) leads to neutrophil infiltration and neutrophil extracellular trap (NET) formation in the liver. Further research shows that NET formation is associated with the reactive oxygen species (ROS)-NLRP3 axis. Inhibition of ROS and NLRP3 can alleviate PSNP-induced NET formation. Moreover, the use of DNase I-coated PSNPs can disassemble NET, reduce neutrophil infiltration in the liver, inhibit the ROS-NLRP3 axis, and decrease cytokine expression.