The mechanism underlying correlation of particulate matter-induced ferroptosis with inflammasome activation and iron accumulation in macrophages.
Minkyung ParkSujeong ParkYumin ChoiYoung-Lai ChoMin Jeong KimYoung Jun ParkSu Wol ChungHeedoo LeeSeon-Jin LeePublished in: Cell death discovery (2024)
Particulate matter (PM) is a global environmental hazard, which affects human health through free radical production, cell death induction, and immune responses. PM activates inflammasomes leading to excessive inflammatory responses and induces ferroptosis, a type of cell death. Despite ongoing research on the correlation among PM-induced ferroptosis, immune response, and inflammasomes, the underlying mechanism of this relationship has not been elucidated. In this study, we demonstrated the levels of PM-induced cell death and immune responses in murine macrophages, J774A.1 and RAW264.7, depending on the size and composition of particulate matter. PM 2.5 , with extraction ions, induced significant levels of cell death and immune responses; it induces lipid peroxidation, iron accumulation, and reactive oxygen species (ROS) production, which characterize ferroptosis. In addition, inflammasome-mediated cell death occurred owing to the excessive activation of inflammatory responses. PM-induced iron accumulation activates ferroptosis and inflammasome formation through ROS production; similar results were observed in vivo. These results suggest that the link between ferroptosis and inflammasome formation induced by PM, especially PM 2.5 with extraction ions, is established through the iron-ROS axis. Moreover, this study can effectively facilitate the development of a new therapeutic strategy for PM-induced immune and respiratory diseases.
Keyphrases
- particulate matter
- cell death
- air pollution
- immune response
- cell cycle arrest
- high glucose
- diabetic rats
- reactive oxygen species
- human health
- risk assessment
- heavy metals
- drug induced
- dna damage
- polycyclic aromatic hydrocarbons
- body mass index
- endothelial cells
- quantum dots
- toll like receptor
- climate change
- oxidative stress
- water soluble
- dendritic cells
- signaling pathway
- weight loss
- weight gain
- fatty acid
- iron deficiency