Chronic lung inflammation and pulmonary fibrosis after multiple intranasal instillation of PM2.5 in mice

Fine particulate matter (PM2.5) is an important component of air pollution and can induce lung inflammation and oxidative stress. We hypothesized that PM2.5 could play a role in the induction of pulmonary fibrosis. We examined whether multiple intranasal instillation of PM2.5 can induce pulmonary fibrosis in the mouse, and also investigated the underlying pro-fibrotic signaling pathways. C57/BL6 mice were intranasally instilled with 50 mu l of PM2.5 suspension (7.8 mu g/g body weight) or PBS three times a week over 3 weeks, 6 weeks or 9 weeks. To observe the recovery of pulmonary fibrosis after the termination of PM2.5 exposure, 9 week-PM2.5 instilled mice were also studied at 3 weeks after termination of instillation. There were significant decreases in total lung capacity (TLC) and compliance (Cchord) in the 9-week PM2.5-instilled mice, while there were increased histological fibrosis scores with enhanced type I collagen and hydroxyproline deposition, increased mitochondrial ROS levels and NOX activity, decreased total SOD and GSH levels, accompanied by decreased mitochondrial number and aberrant mitochondrial morphology (swelling, vacuolization, cristal disruption, reduced matrix density) in PM2.5-instilled mice. Multiple PM2.5 instillation resulted in increased expression of TGF beta 1, increases of N-Cadherin and Vimentin and a decrease of E-Cadherin. It also led to decreases in OPA1 and MFN2, and increases in Parkin, SQSTM1/p62, the ratio of light china (LC) 3B II to LC3B I, PI3k/Akt phosphorylation, and NLRP3 expression. Intranasal instillation of PM2.5 for 9 weeks induced lung inflammation and pulmonary fibrosis, which was linked with aberrant epithelial-mesenchymal transition, oxidative stress, mitochondrial damage and mitophagy, as well as activation of TGF beta 1-PI3K/Akt, TGF beta 1- NOX and TGF beta 1-NLRP3 pathways.

Automated summary

Repeated intranasal instillation of PM2.5 induced lung inflammation, oxidative stress, mitochondrial damage, and pulmonary fibrosis in mice.