Mechanism of PM2.5-induced human bronchial epithelial cell toxicity in central China.

Exposure to PM2.5 has been linked to respiratory disorders, yet knowledge of the molecular mechanism is limited. Here, PM2.5 was monitored and collected in central China, and its cytotoxicity mechanism on human bronchial epithelial cells (BEAS-2B) was investigated. With the average concentration of 109 ± 69 μg/m3, PM2.5 was rich in heavy metals and organic pollutants. After exposure to PM2.5, the viability of BEAS-2B cells decreased, where 510 dysregulated genes were predicted to induce necroptosis via inhibiting ATP synthesis through the oxidative phosphorylation signaling pathway. Cellular experiments demonstrated that the content of ATP was downregulated, while the expression of RIP3, a necroptosis indicator, was upregulated. Besides, four enzymes in charge of ATP synthesis were downregulated, including ATP5F, NDUF, COX7A, and UQCR, while two genes of RELA and CAPN1 responsible for necroptosis were upregulated. Furthermore, N-acetylcysteine was applied as an enhancer for ATP synthesis, which reversed the downregulation of ATP5F, NDUF, and COX7A, and consequently alleviated the elevation of RELA, CAPN1, and RIP3. In conclusion, PM2.5 exposure downregulates ATP5F, NDUF, COX7A, and UQCR, and that inhibits ATP synthesis via the oxidative phosphorylation signaling pathway, which subsequently upregulates RELA and CAPN1 and ultimately leads to necroptosis of BEAS-2B cells.