Abstract
BackgroundNanomaterial inhalation represents a potential hazard for respiratory conditions such as asthma. Cerium dioxide nanoparticles (CeO2NPs) have the ability to modify disease outcome but have not been investigated for their effect on models of asthma and inflammatory lung disease. The aim of this study was to examine the impact of CeO2NPs in a house dust mite (HDM) induced murine model of asthma.ResultsRepeated intranasal instillation of CeO2NPs in the presence of HDM caused the induction of a type II inflammatory response, characterised by increased bronchoalveolar lavage eosinophils, mast cells, total plasma IgE and goblet cell metaplasia. This was accompanied by increases in IL-4, CCL11 and MCPT1 gene expression together with increases in the mucin and inflammatory regulators CLCA1 and SLC26A4. CLCA1 and SLC26A4 were also induced by CeO2NPs + HDM co-exposure in air liquid interface cultures of human primary bronchial epithelial cells. HDM induced airway hyperresponsiveness and airway remodelling in mice were not altered with CeO2NPs co-exposure. Repeated HMD instillations followed by a single exposure to CeO2NPs failed to produce changes in type II inflammatory endpoints but did result in alterations in the neutrophil marker CD177. Treatment of mice with CeO2NPs in the absence of HDM did not have any significant effects. RNA-SEQ was used to explore early effects 24 h after single treatment exposures. Changes in SAA3 expression paralleled increased neutrophil BAL levels, while no changes in eosinophil or lymphocyte levels were observed. HDM resulted in a strong induction of type I interferon and IRF3 dependent gene expression, which was inhibited with CeO2NPs co-exposure. Changes in the expression of genes including CCL20, CXCL10, NLRC5, IRF7 and CLEC10A suggest regulation of dendritic cells, macrophage functionality and IRF3 modulation as key early events in how CeO2NPs may guide pulmonary responses to HDM towards type II inflammation.ConclusionsCeO2NPs were observed to modulate the murine pulmonary response to house dust mite allergen exposure towards a type II inflammatory environment. As this type of response is present within asthmatic endotypes this finding may have implications for how occupational or incidental exposure to CeO2NPs should be considered for those susceptible to disease.
Highlights
Nanomaterial inhalation represents a potential hazard for respiratory conditions such as asthma
While it is clear that Cerium dioxide nanoparticle (CeO2NP) appear to have a detrimental effect on lung health in healthy animals, little information exists on how CeO2NPs may influence susceptible lung conditions such as COPD and asthma
CeO2NPs used in this study have been reported by the manufacturer as having an average primary particle size of < 25 nm
Summary
Nanomaterial inhalation represents a potential hazard for respiratory conditions such as asthma. Exposure to CeO2NPs in the absence of underlying disease processes appears to result in toxicological effects, such as disruption of microvascular smooth muscle signalling [9], systemic organ toxicity [10] and potential genotoxicity [11, 12]. These observations of active biological interaction have led to concerns over whether CeO2NPs may pose a health hazard as a result of incidental or occupational exposure. While it is clear that CeO2NPs appear to have a detrimental effect on lung health in healthy animals, little information exists on how CeO2NPs may influence susceptible lung conditions such as COPD and asthma
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