Indium tin oxide nanoparticles induce interleukin-1β-mediated epithelial-mesenchymal transition in alveolar epithelial cells

抄録

Indium tin oxide (ITO) is one of the most widely manufactured materials with broad applications, such as flat panel displays, touch panels, and solar panels. Whereas cases of indium-related lung disease, such as pulmonary emphysema and fibrosis, have been reported worldwide, the effects of ITO on the progression of epithelial-mesenchymal transition (EMT) are completely unknown. EMT is a crucial process whereby fully differentiated cells undergo morphological changes from the epithelial phenotype to the mesenchymal phenotype and is associated with pulmonary fibrosis. The purpose of this study was to understand the inductive mechanism of indium-related lung diseases, focusing on the fibrotic potential of ITO nanoparticles (NPs) through EMT induction. We found that a conditioned medium obtained from THP-1-derived macrophages stimulated with ITO NPs induced morphological changes, high motility, and EMT progression in A549 cells. Furthermore, we identified that interleukin-1β (IL-1β) is an ITO NP-mediated EMT inducer based on the results of cytokine array as well as cellular physiological and biochemical analysis. In addition, we found that IL-1β-exposed cells co-expressed epithelial and mesenchymal markers and abolished the proper localization of cell-cell junction-related proteins, which is similar to the partial EMT phenotype. Taken together, these findings suggest that IL-1β is released from macrophages stimulated with ITO NPs and is able to induce EMT progression in alveolar epithelial cells, thereby potentially triggering the genesis and development of pulmonary fibrosis.