8-Bromo-cAMP attenuates human airway epithelial barrier disruption caused by titanium dioxide fine and nanoparticles.

Titanium dioxide fine particles (TiO-FPs) and nanoparticles (TiO-NPs) are the most widely used whitening pigments worldwide. Inhalation of TiO-FPs and TiO-NPs can be harmful as it triggers toxicity in the airway epithelial cells. The airway epithelium serves as the respiratory system's first line of defense in which airway epithelial cells are significant targets of inhaled pathogens and environmental particles. Our group previously found that TiO-NPs lead to a disrupted barrier in the polarized airway epithelial cells. However, the effect of TiO-FPs on the respiratory epithelial barrier has not been examined closely. In this study, we aimed to compare the effects of TiO-FPs and TiO-NPs on the structure and function of the airway epithelial barrier. Additionally, we hypothesized that 8-Bromo-cAMP, a cyclic adenosine monophosphate (cAMP) derivative, would alleviate the disruptive effects of both TiO-FPs and TiO-NPs. We observed increased epithelial membrane permeability in both TiO-FPs and TiO-NPs after exposure to 16HBE cells. Immunofluorescent labeling showed that both particle sizes disrupted the structural integrity of airway epithelial tight junctions and adherens junctions. TiO-FPs had a slightly more, but insignificant impact on the epithelial barrier disruption than TiO-NPs. Treatment with 8-Bromo-cAMP significantly attenuated the barrier-disrupting impact of both TiO-FPs and TiO-NPs on cell monolayers. Our study demonstrates that both TiO-FPs and TiO-NPs cause comparable barrier disruption and suggests a protective role for cAMP signaling. The observed effects of TiO-FPs and TiO-NPs provide a necessary understanding for characterizing the pathways involved in the defensive role of the cAMP pathway on TiO-induced airway barrier disruption.