Assessing the Adverse Impacts of PM_2.5 on Olfactory System Using an Air-liquid Interface Culture Model of Primary Olfactory Epithelial Cells

Abstract

The air-liquid interface(ALI) culture is a kind of recently developed system, which has proved its availability in simulating the biology of respiratory tract epithelial tissues. In this study, an ALI-based mouse primary olfactory epithelial cell(OEC) model was established to perform the exposure of PM_2.5 (PM=particulate matter) collected from Dianshan Lake(Shanghai) and Wangdu(Hebei). The results showed that PM_2.5 in both regions caused a decrease in cell viability in a dose-dependent manner. The 0.5 and 5 µg/cm²(around ambient concentrations) of PM_2.5 disrupted OEC membrane integrity and produced oxidative stress with elevated indicators of malondialdehyde(MDA) and reactive oxygen species(ROS). In transcriptomic sequencing, the terms concerning inflammatory cytokines and second messenger cyclic adenosine-3′,5′-monophoshate(cAMP) were enriched in two treatments. The cytokine array showed the levels of some cytokines were altered, although inflammatory responses may not remarkably occur. Meanwhile, PM_2.5 disturbed cAMP contents and key genes in the cAMP signaling pathway. The effects of PM_2.5 of both regions were largely consistent, while Wangdu samples caused more ROS and Dianshan Lake samples tended to induce inflammatory injury. Thus, with the application of a novel ALI-based in vitro OEC model, our study demonstrated that ambient PM_2.5 has the ability to threaten the physiologies and functions of the olfactory system.

Keywords

Air-liquid interface / Olfactory epithelial cell / PM_2.5 / Inflammatory cytokines / Cyclic adenosine-3′,5′-monophoshate (cAMP)

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