Allergy Asthma Immunol Res.  2017 May;9(3):257-264. 10.4168/aair.2017.9.3.257.

Effect of TiOâ‚‚ Nanoparticles on Inflammasome-Mediated Airway Inflammation and Responsiveness

• Kim BG
• Lee PH
• Lee SH
• Park MK
• Jang AS

• KMID: 2371726
• DOI: http://doi.org/10.4168/aair.2017.9.3.257

Abstract

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-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 TiOâ‚‚ 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.

Keyword

Titanium dioxide; inflammasome; bronchial asthma

MeSH Terms

Animals
Asthma
Blotting, Western
Caspase 1
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Inflammasomes
Inflammation*
Inhalation
Interleukin-18
Lung
Mice
Nanoparticles*
Ovalbumin
Particulate Matter
Reactive Oxygen Species
Titanium
Caspase 1
Inflammasomes
Interleukin-18
Ovalbumin
Particulate Matter
Reactive Oxygen Species
Titanium

Figure

• 

  Fig. 1 Experiment protocol of TiO2 NPs exposure model.

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  Fig. 2 Airway responsiveness to methacholine in OVA-exposed mice group and TiO2 NPs exposed mice group, and OVA plus TiO2 NPs exposed mice group. *P<0.05 OVA, TiO2 NPs vs Sham; †OVA vs OVA plus TiO2 NPs.

• 

  Fig. 3 Differential cell count in bronchoalveolar lavage fluid in OVA-exposed mice group and TiO2 NPs exposed mice group, and OVA plus TiO2 NPs exposed mice group. *P<0.05 OVA, TiO2 NPs vs Sham; †OVA vs OVA plus TiO2 NPs.

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  Fig. 4 Lung NLRP3, IL-18, and IL1β protein levels in OVA-exposed mice group and TiO2 NPs exposed mice group, and OVA plus TiO2 NPs exposed mice group. *P<0.05 OVA, TiO2 NPs vs Sham; †OVA vs OVA plus TiO2 NPs.

• 

  Fig. 5 Lung activated caspase-1 protein expression by Western blot in OVA-exposed mice group and TiO2 NPs exposed mice group, and OVA plus TiO2 NPs exposed mice group.

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  Fig. 6 Lung caspase-1 protein expression by Hematoxylin and eosin (H&E), and immunohistochemical stain in OVA-exposed mice group and TiO2 NPs exposed mice group, and OVA plus TiO2 NPs exposed mice group. *P<0.05 OVA, TiO2 NPs vs Sham; †OVA vs OVA plus TiO2 NPs.

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  Fig. 7 Oxidative damage markers and mediators 8-isoprotane and carbonyl lung levels by ELISA in OVA-exposed mice group and TiO2 NPs exposed mice group, and OVA plus TiO2 NPs exposed mice group.

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  Fig. 8 TiO2 NPs induced inflammasome IL-1β and IL-18-airway hyperresponsiveness and inflammation.

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