Mitochondrial dysfunction and inflammatory response in the cytotoxicity of NR8383 macrophages induced by fine particulate matter.

Exposure to fine particulate matter (fine PM) is known to cause severe public health problems. However, the potential mechanisms of alveolar macrophages cytotoxicity induced by fine PM exposure are still unclear. The aim of this study was to determine if both the mitochondrial dysfunction and the inflammatory response of NR8383 macrophages were triggered by Standard Reference Material 2786 (SRM 2786) for fine PM. NR8383 cells were exposed to different concentrations of SRM 2786, mitochondrial membrane potential, ultrastructure of mitochondria, activities of caspase 3/9, release of IL-6/TNF-α, expression of NF-κB and IκBα were evaluated. The results indicated that SRM 2786 induced mitochondrial dysfunction by increasing activities of caspase-3 and caspase-9, and structural damages of mitochondria with dissipation of mitochondrial membrane potential. The inflammatory response was triggered as evidenced by increased release of IL-6/TNF-α, and increased protein expression of NF-κB with decreased protein expression of IκBα. Consequently, these data indicate that both mitochondrial dysfunction and inflammatory responses might be responsible for SRM 2786 induced macrophage cytotoxicity.