Cerium dioxide nanoparticle and diesel particulate inhalation: modifying potential on models of asthma and allergen exposure

Abstract

Concerns have been raised regarding possible health effects due to constituents of air pollution, including increasing diesel use and addition of fuel catalysts such as cerium dioxide nanoparticles (CeO2NPs). There is limited information on the potential hazards of this nanomaterial as part of diesel exhaust on respiratory conditions, including asthma and allergic airway disease (AAD). We therefore aimed to identify the effects of diesel exhaust particles (DEP) alone and in combination with CeO2NPs in both an in vitro lung epithelial model and an in vivo murine house dust mite (HDM) model of AAD. Human primary bronchial epithelial cells (HPBECs) and Balb/c mice were exposed via a quasi-air liquid interface or intranasally to HDM alone or with DEP (50µg) alone or combined with low (50ng) or high (1.5µg) concentrations of CeO2NPs in single and repeat dose protocols over 24 hours and 3 weeks. HPBECs DEP exposure leads to increases in type II immune response mRNA expression when compared to co-exposure (CeO2NPs/DEP), while IL-25 expression was significantly increased after CeO2NPs/DEP exposure compared to particles alone and control. Within the murine AAD model, the addition of DEP to HDM (over 3 weeks) caused an increase in the inflammatory cell counts (specifically lymphocytes, macrophages and neutrophils). Addition of CeO2NPs to this combination resulted in a further significant increase in BAL cell counts, specifically lymphocytes and eosinophils. This was also paralleled by CeO2NPs dependent alterations in inflammatory gene expression, as well as an increase in mucus production, airway remodelling and hyperresponsiveness when compared to DEP, CeO2NPs alone and the HDM control. This taken together suggests that the addition of CeO2NPs has the potential to modify DEP effects and enhance an allergic response within a murine AAD model. This has the potential to have impacts within the asthmatic population as these catalysts increase in popularity.