Development of a Novel Air-Liquid Interface Exposure System for Particle Exposure in Alveolar Epithelium

抄録

With the global trend towards the abolition of animal testing, there is an increasing demand for improving alternative methods for particulate matter (PM) inhalation toxicity assessment. In the present study, we developed a novel aerosol exposure system for alveolar cells using an atomizer. The humidity in the exposure chamber was maintained at 95%. When Calu-3 human lung epithelial cells were exposed to urban PM (CRM28) for 1 h and then cultured in an incubator under a CO₂ atmosphere, time-dependent decreases in the transepithelial electrical resistance and cell viability were observed. Interleukin-25 (IL-25) expression increased, whereas claudine18 (CLDN18) expression decreased in Calu-3 cells following CRM28 exposure. When mice were intranasally exposed to CRM28 or PM2.5, collected in Yokohama, Japan, for 7 days, increased IL-25 expression and decreased CLDN18 expression were observed in the lung tissues. Changes in the expression of IL-25 and CLDN18 were also observed in the lungs of mice stimulated with ovalbumin. Taken together, the exposure chamber developed in this study allowed aerosol exposure to cultured alveolar epithelial cells at humidity levels similar to those found in alveoli, and IL-25 and CLDN18 may be used as markers for respiratory damage caused by PM exposure.