Lung inflammation caused by long-term exposure to titanium dioxide in mice involving in NF-κB signaling pathway

Titanium dioxide nanoparticles (TiO₂ NPs) are used in many fields, such as paints, medicine additives, food additives, sunscreens, and agriculture. The aim of this study was to investigate the mechanism behind the formation of inflammation induced by TiO₂ NPs. ICR mice were exposed to TiO₂ NPs through intragastric administration at 2.5, 5, and 10 mg/kg body weight every day for 90 consecutive days. The experiment suggested that long-term exposure to TiO₂ NPs resulted in an obvious inflammatory response in mice lung tissues, which led to a thickened alveoli septum, lung hyperemia, and titanium accumulation. Furthermore, our results show that TiO₂ NPs exposure remarkably altered the expression of inflammation-related cytokines, with increases in proinflammatory cytokines—such as nucleic factor-κB, interferon-α, interferon-β, interleukin-1β, interleukin-6, cyclo-oxygen-ase, interleukin-8, interferon-inducible protein-10, and platelet-derived growth factor AB—and decreases in anti-inflammatory cytokines—such as inhibitor of NF-κB suppressor of cytokine signaling 1, endothelin 1, peroxisome proliferators-activated receptors-γ, and peroxisome proliferators-activated receptors coactivator-1α. This finding indicated that TiO₂ NPs cause lung inflammation in mice after intragastric administration, primarily through the NF-κB signaling pathways. Therefore, more attention should be placed on the application of TiO₂ NPs and their potential long-term effects, especially in human beings. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 720–727, 2017.