SiO2 dust induces inflammation and pulmonary fibrosis in rat lungs through activation of ASMase/Ceramide pathway.

Abstract

The role of ASMase/Ceramide signaling pathway in the development of silicosis needs to be verified by in vivo experiments. We investigated the role of the ASMase/Ceramide signaling pathway in the progression of silicosis and the effect of desipramine (DMI)(1mg/mL) on the development of silicosis, by establishing a silica(1mL, 50mg/mL) dust-contaminated rat silicosis model and administering the ASMase inhibitor, DMI, to the dust-contaminated rats. The results showed that levels of IL-1β and IL-6 were increased in the lung tissues of the rats in the dust-contaminated group at the initial stage after dusting, the inflammatory cell aggregation in the lung tissue was increased. With time progression, the hydroxyproline content in the lung tissue increased, and α-SMA, collagen I and vimentin substantially increased, suggesting that silicosis were formed in the lung tissue of the rats 28 days after SiO2 dust treatment. Moreover, the levels of ASMase, ceramide and S1P were increased in the lung tissue of rats. The expression of β-catenin, fibronectin and caspase-3 protein was increased, and E-cadherin protein expression was decreased in the lung tissue of the rats in the late stage of dust contamination. The ASMase and ceramide in the lung tissues of the rats in the DMI intervention group were reduced, as were the lung tissue inflammation levels, collagen expression, and lung fibrosis. These results suggest that SiO2 dust may activate the ASMase/ceramide signaling pathway in rat lung tissue, promoting pulmonary fibrosis. DMI inhibited these activation, attenuated apoptosis and blocked epithelial-mesenchymal transition and halted silica dust-induced silicofibrosis.