Macrophage-amplified toxicity of indium tin oxide nanoparticles to bronchial epithelial cells involving ROS-associated NF-κB signaling.

Source: PubMed, NCBI / U.S. National Library of Medicine

Indium tin oxide nanoparticles (ITO NPs) are widely used in optoelectronic industries, and increasing occupational exposure has raised concern about their pulmonary toxicity. Although ITO exposure has been associated with severe lung diseases, the mechanisms underlying epithelial injury remain unclear. Here, a simplified macrophage-epithelial cell model using RAW264.7 macrophages and BEAS-2B epithelial cells was established to investigate how macrophages modulate ITO NP-induced epithelial toxicity. Direct exposure to ITO NPs caused limited toxicity in BEAS-2B cells, whereas conditioned medium from ITO NP-exposed RAW264.7 cells was associated with reduced epithelial viability, increased LDH release, and EMT-like changes. Dissolved indium species alone did not fully account for the observed effects, whereas macrophage-derived oxidative stress and associated inflammatory responses appeared to contribute more substantially to the epithelial responses. Transcriptomic and biochemical analyses showed that ITO NPs induced oxidative stress and activated NF-κB signaling in macrophages. Inhibition of ROS or NF-κB attenuated macrophage-derived cytotoxicity and reduced EMT-like changes in epithelial cells. These findings support a role for macrophages as important regulators of ITO NP-induced epithelial injury and provide additional mechanistic insight into ITO-related pulmonary toxicity.