Exploration of potential mechanism of interleukin-33 up-regulation caused by 1,4-naphthoquinone black carbon in RAW264.7 cells

Background: As air pollution has been paid more attention to by public in recent years, effects and mechanism in particulate matter-triggered health problems become a focus of research. Lysosomes and mitochondria play an important role in regulation of inflammation. Interleukin-33 (IL-33) has been proved to promote inflammation in our previous studies. In this research, macrophage cell line RAW264.7 was used to explore the potential mechanism of upregulation of IL-33 induced by 1,4-naphthoquinone black carbon (1,4-NQ-BC), and to explore changes of lysosomes and mitochondria during the process. Results: 50 mu g/mL 1,4-NQ-BC exposure for 24 h dramatically increased expression of IL-33 in RAW264.7 cells. Lysosomal membrane permeability was damaged by 1,4-NQ-BC treatment, and higher mitochondrial membrane potential and ROS level were induced by 1,4-NQ-BC. The results of proteomics suggested that expression of ferritin light chain was increased after cells were challenged with 1,4-NQ-BC, and it was verified by Western blot. Meanwhile, expressions of p62 and LC3B-II were increased by 50 mu g/mL 1,4-NQ-BC in RAW264.7 cells. Ultimately, expression of IL-33 could return to same level as control in cells treated with 50 mu g/mL 1,4-NQ-BC and 50 mu M deferoxamine combined. Conclusions: 1,4-NQ-BC induces IL-33 upregulation in RAW264.7 cells, and it is responsible for higher lysosomal membrane permeability and ROS level, lower mitochondrial membrane potential, and inhibition of autophagy. Ferritin light chain possibly plays an important role in the upregulation of IL-33 evoked by 1,4-NQ-BC.

Automated summary

This study found that 1,4-naphthoquinone black carbon (1,4-NQ-BC) treatment led to upregulation of interleukin-33 (IL-33) in macrophage cell line RAW264.7. 1,4-NQ-BC treatment damaged lysosomal membrane permeability and induced higher mitochondrial membrane potential and ROS level. Proteomic analysis showed that expression of ferritin light chain increased after cells were challenged with 1,4-NQ-BC. These findings suggest that 1,4-NQ-BC may induce IL-33 upregulation through mechanisms involving higher lysosomal membrane permeability and ROS level, lower mitochondrial membrane potential, and inhibition of autophagy.