Involvement of the JNK/HO-1/FTH1 signaling pathway in nanoplastic-induced inflammation and ferroptosis of BV2 microglia cells

Nanoplastics (NPs) are a newly discovered type of environmental pollutant. The potential for neurotoxicity caused by NPs and their mechanisms are unclear. The present study aimed to determine the molecular mechanism underlying neurotoxicity induced by NPs. Microglia (BV2) cells were used for in vitro studies, and it was found that NPs invaded cells, activated inflammasomes, induced the release of significant quantities of inflammatory factors by detection of inflammatory response-associated proteins through Western blot and ELISA. By detection of FITC, SOD, GSH, cellular iron level, and ferroptosis-related proteins, it was found that NPs compromised the anti-oxidative mechanisms of cells, increased intracellular lipid peroxidation and Fe2+ concentration and triggered inflammatory reactions and ferroptosis. Pretreatment with reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC) alleviated induction of inflammatory reactions and ferroptosis of cells. In addition, inhibiting expression of c-Jun N-terminal kinase (JNK) increased expression of heme oxygenase (HO-1), resulting in decreased ferroptosis, indicating that the JNK/HO-1 signaling pathway was involved in NP-induced effects on ferroptosis in BV2 cells. In conclusion, NPs could induce inflammatory responses and ferroptosis in BV2 cells. JNK/HO-1 mediated ferroptosis may serve an important role in the toxicity of microglia induced by NPs. This study provided novel evidence for the toxic effects of NPs and highlighted a theoretical mechanistic basis for safe prevention and treatment of plastic pollution-induced neurotoxicity.

Automated summary

This study found that nanoplastics can induce inflammation and ferroptosis in BV2 cells, and inhibiting the JNK/HO-1 pathway can alleviate their toxic effects on cells.