Sestrin2/Keap1/Nrf2 pathway regulates mucus hypersecretion in pulmonary epithelium induced by traffic-related PM2.5 and water-soluble extracts

The involvement of fine particulate matter (PM2.5) exposure in the progression of asthma has been extensively discussed in epidemiological and experimental evidence, which aroused widespread attention. Asthma is characterized by mucus hypersecretion. This study investigates the underlying toxic mechanism of traffic-related PM2.5 (TRPM2.5) and water-soluble extracts (WSE) on mucus hypersecretion in the lungs of rats with asthma and 16HBE cells. The ovalbumin-induced rats were administrated by instillation of TRPM2.5 and WSE in the trachea once three days for eight times. The results showed that TRPM2.5 and WSE had an adverse impact on mucus secretion. Specifically, conspicuous mucus stains and increased goblet cells in the bronchial epithelium by PAS staining were found in lung tissues of rats with asthma; MUC5AC gene and protein expression levels in lung tissues of rats with asthma and 16HBE cells were elevated. In addition, TRPM2.5 and WSE triggered oxidative damage via upregulation of malondialdehyde and myeloperoxidase as well as activation of the Sestrin2/Keap1/Nrf2 signaling pathway. Conversely, the knockdown of Sestrin2 effectively inhibited TRPM2.5 and WSE-induced mucus hypersecretion, oxidative stress, and Keap1/Nrf2 signaling pathway and its downstream target gene NQO1. Collectively, it was demonstrated that TRPM2.5 and WSE induced mucus hypersecretion mediated by the Sestrin2/Keap1/Nrf2 pathway.