Effect of TiO2 Nanoparticles on Inflammasome-Mediated Airway Inflammation and Responsiveness

Purpose: Nanoparticles (NPs) may cause cell and tissue damage, leading to local and systemic inflammatory responses and adverse effects on health due to the inhalation of particulate matter. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1 beta (pro-IL-1 beta) into its mature form and may induce acute and chronic immune responses to NPs. However, little is known about the response of the inflammasome to NP exposure via the airways in asthma. The aim of this study was to identify the impact of titanium dioxide (TiO2) NPs on inflammasome in a mouse model of allergic asthma. Methods: Mice were treated with ovalbumin (OVA) or TiO2 NPs. IL-1 beta, IL-18, NAIP, CIITA, HET-E, TP-2 (NACHT), leucine-rich repeat (LRR), pyrin domain-containing protein 3 (NLRP3), and caspase-1 were assessed by Western blotting. Caspase-1 was assessed by immunohistochemistry (INC). Levels of reactive oxygen species (ROS) as.markers of oxidative damage and the mediators 8-isoprostane and carbonyl were measured by enzyme-linked immunosorbent assay (ELISA). Results: Airway hyperresponsiveness (AHR) and inflammation were increased in OVA-sensitized/challenged mice, and these responses were exacerbated by exposure to TiO2 NPs. NP treatment increased IL-1 beta and IL-18 expression in OVA-sensitized/challenged mice. NPs augmented the expression of NLRP3 and caspase-1, leading to production of active caspase-1 in the lung. Caspase-1 expression was increased and exacerbated by TiO2 NP exposure in OVAsensitized/challenged mice. ROS levels tended to be increased in OVA-sensitized/challenged and OVA-sensitized/challenged-plus-TiO2 NP-exposed mice. Conclusions: Our data demonstrated that inflammasome activation occured in asthmatic lungs following NP exposure, suggesting that targeting the inflammasome may assist in controling NP-induced airway inflammation and hyperresponsiveness.