Short-term PM2.5 exposure induces sustained pulmonary fibrosis development during post-exposure period in rats.

Up to now, while some toxicological studies have identified pulmonary fibrosis immediately induced by long-term PM2.5 exposure, there has been no evidence indicating, whether short-term exposure can lead to post-exposure development of pulmonary fibrosis. Here, we treated rats with PM2.5 for 1 month (10 times), followed by normal feeding for 18 months. 18F-FDG intake, which is linked with the initiation and development of pulmonary fibrosis in living bodies, was found to gradually increase in lung following exposure through micro PET/CT imaging. Histolopathological examination revealed continuous deterioration of pulmonary injury post-exposure. Collagen deposition and hydroxyproline content continued to increase all along in the post-exposure duration, indicating pulmonary fibrosis development. Chronic and persistent induction of pulmonary inflammatory gene expression (Tnf, Il1b, Il6, Ccl2, and Icam1), epithelial mesenchymal transition (EMT, reduction of E-cadherin and elevation of fibronectin) and RelA/p65 upregulation, as well as serum inflammatory cytokine production, were also found in PM2.5-treated rats. Pulmonary oxidative stress, manifested by increase of MDA and decrease of GSH and SOD, was induced during exposure but disappeared in later post-exposure duration. These results suggested that short-term PM2.5 exposure could lead to sustained post-exposure pulmonary fibrosis development, which was mediated by oxidative-stress-initiated NF-κB/inflammation/EMT pathway.