Effects of cerium oxide nanoparticles on fibroblast function in relation to lung fibrosis.
Ma JY; Hines B; Barger M; Mercer RR; Castranova V
Toxicologist 2013 Mar; 132(1):505-506
The emission of cerium oxide nanoparticles (CeO2 ) in the diesel exhaust, when cerium compounds were used as a diesel engine catalyst to lower the diesel exhaust particles, is a health concern. Our previous studies have shown that CeO2 induced pulmonary inflammation and lung fibrosis. The objective of the present study is to investigate the modification of fibroblast function by CeO2 in relation to fibrosis. Male Sprague Dawley rats were exposed to CeO2 (0.15 to 7 mg/kg) by a single intratracheal instillation and sacrificed at various times post exposure. Alveolar macrophages (AM) were isolated by bronchoalveolar lavage (BAL), and lung fibroblasts were isolated from the lung tissues. The first BAL fluid and AM culture medium obtained after a 24 h incubation time were saved for further analysis. The results show that at 28 days after CeO2 (3.5 mg/kg) exposure, lung fibrosis was evident by increased hydroxyproline content in lung tissues and enhanced Sirius Red staining collagen fibers in the lung. In addition, the presence of stress actin, expressed as alpha-smooth muscle actin (SMA), in fibroblasts was also significantly increased when compared to the control. Lung fibroblasts isolated from CeO2-exposed rats at 28 days post-exposure showed a dose-dependent decrease in proliferation rate using the MTT assay. Treating primary fibroblasts with CeO2 in vitro, did not significantly affect cell proliferation rate; however, when treated with the first BAL fluid collected at 3- or 10-days after CeO2 exposure, significantly increased cell proliferation when compared to the control. In vitro treatment of fibroblasts with TGF-beta1 significantly increased alpha-SMA expression. These results demonstrate that CeO2 induces a dirverse network of mediators that affects fibroblast proliferation and functional changes that may play a role in lung fibrosis. These findings suggest potential health effects of CeO2 exposure.
Toxicology; Nanotechnology; Laboratory-animals; Laboratory-testing; Exposure-assessment; Exposure-levels; Pulmonary-system; Dose-response; Lung-fibrosis; Cerium-compounds; Oxides; Lung-cells; Alveolar-cells; Cell-function; Cellular-reactions; Lung-tissue; Fibrosis; Collagen-fibrils; In-vitro-study; Bioassays; Nanotechnology; Laboratory-animals; Exposure-levels; Inhalation-studies; Diesel-emissions; Diesel-exhausts; Hazardous-materials; Liver; Liver-cells; Lung; Lung-cells; Immune-system; Immune-reaction; Oxidative-processes; Cellular-reactions; Antioxidants; Myeloid-tissue; Peroxidases; Carbonyls; Thiols; Proteins; Lung-tissue; Cellular-function; Fuels; Biomarkers; Hydroxy-compounds; Cytotoxic-effects; Liver-damage; Liver-tissue; Lung-tissue; Molecular-biology
Transportation, Warehousing and Utilities
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas