The role of ferroptosis mediated by NRF2/ERK-regulated ferritinophagy in CdTe QDs-induced inflammation in macrophage

Cadmium telluride quantum dots (CdTe QDs) exist in the environment due to the abandonment of products. There is a potential risk to organisms and toxic mechanism is worth exploring. In this study, 12.5 mu mol/Kg body weight CdTe QDs triggered systemic and local inflammatory response in mice and activated macrophages, then the mechanism of activating macrophages to overexpress IL-1 beta and IL-6 was explored. RAW264.7 macrophages were used, and after macrophages exposing to 1 mu M CdTe QDs for 24 h, oxidative stress occurred. Further investigation found that CdTe QDs triggered ferroptosis in RAW264.7 cells. And deferoxamine mesylate allevi-ated the excessive lipid hydroperoxide caused by QDs. Mechanistically, CdTe QDs-provoked decrease of nuclear factor erythroid 2-related factor 2 (NRF2) elicited phosphorylation of extracellular regulated protein kinases1/2 (ERK1/2) and then activated ferritinophagy, which made ferritin heavy chain 1 (FTH1) degraded in lysosome and proteasome to release free iron ions to initiate ferroptosis in macrophages. This paper updates the mecha-nism of macrophage activation by CdTe QDs with regard to ferritinophagy, and more importantly, identifies the key role of NRF2 and ERK1/2. Our research extends the role of ferroptosis in inflammatory responses triggered by nanoparticles (NPs) in macrophages and provides insightful reference for toxicity assessment of NPs.

Automated summary

Cadmium telluride quantum dots (CdTe QDs) trigger inflammatory responses and activate macrophages in mice, and the mechanism behind the activation of macrophages to overexpress IL-1 beta and IL-6 is explored. The study reveals that CdTe QDs induce ferroptosis in macrophages. Activation of ferritinophagy through a decrease in NRF2 and phosphorylation of ERK1/2 plays a key role in initiating ferroptosis in macrophages.