title: Effect of TiO₂ Nanoparticles on Inflammasome-Mediated Airway Inflammation and Responsiveness.
abstract: OBJECTIVE
  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-1β (pro-IL-1β) 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-1β, 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 (IHC). 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-1β 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 OVA-sensitized/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.
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Byeong Gon
authors.initials: BG
authors.lastname: Kim
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Pureun Haneul
authors.initials: PH
authors.lastname: Lee
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
authors.forename: Sun Hye
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Otolayngology, Seoul National Uiversity, Seoul, Korea.
authors.forename: Moo Kyun
authors.initials: MK
authors.lastname: Park
authors.affiliation: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea. jas877@schmc.ac.kr.
authors.forename: An Soo
authors.initials: AS
authors.lastname: Jang
keywords: Titanium dioxide; bronchial asthma; inflammasome