(P03-074-23) Aesculetin Suppresses Urban Particulate Matter-Induced Airway Epithelial Abnormality

Objectives: Particulate matter (PM), an air pollutant particles suspended in air, is the most harmful for respiratory systems through easily penetrating into the lungs and blood streams. Aesculetin is a coumarin derivative that is known for anti-inflammatory effects on the immune and vascular diseases. The current study aimed to investigate whether aesculetin inhibited airway epithelial dysfunction caused by urban PM10 (uPM10, particles less than 10 μm).

Methods: For the in vivo experiments, Balb/c mice were supplemented with 10 mg/kg aesculetin by oral gavage while inhaling 6 μg/ml uPM10 for 8 weeks. For the in vitro experiments, human bronchial epithelial cells (BEAS-2B) were treated with 2 μg/ml uPM10 in the absence or presence of 1-20 µM aesculetin.

Results: The uPM10 inhalation induced neutrophil elastase (NE) accumulation and interleukin (IL)-1β secretion in the small airways, which was attenuated by oral administration of 10 mg/kg aesculetin. In addition, aesculetin dose-dependently inhibited uPM10-induced NE expression in BEAS-2B cells. The treatment of aesculetin reduced airway epithelial rigidity caused by uPM10 through diminishing induction of barrier proteins of occludin-1 and ZO-1. Furthermore, uPM10 temporally increased the expression of occludin-1 and ZO-1 in bronchial epithelial cells to 4 days, and then such expression declined. Interestingly, aesculetin further enhanced the expression of these proteins induced by 4 day-exposed uPM10.

Conclusions: Aesculetin may be a promising agent suppressing airway epithelial abnormality caused by urban pollute particulates.

Funding Sources: This research was supported by Basic Science Research Program through National Research Foundation of Korea (NRF) funded by the Ministry of Education (2021R1A6A1A03044501) and by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2022R1A2B5B01001861).