Aesculetin Inhibits TLR4 and EGFR-Mediated Airway Mucus Hypersecretion and Thickening Induced by Urban Particulate Matter

Suyeon Oh, Young-Hee Kang
2021 Current Developments in Nutrition  
Objectives uPM10 is microscopic particles of solid or liquid matter suspended in the air. Particulates are the most harmful form of air pollution due to their ability to penetrate deep into the lungs, blood streams and brain, causing diverse health problems. Mucus hypersecretion is a pathological symptom evoked in the bronchi and bronchioles. Excess mucus production can narrow the airways, limit airflow, and accelerate a decline in lung function. Aesculetin, a major component of Sancho tree and
more » ... of Sancho tree and Chicory, is known to have antioxidant and anti-inflammatory effects in the vascular and immune system. However, its effect on mucus hypersecretion has been poorly understood. Methods Mice were orally administrated with 10 mg/kg aesculetin and exposed to 6 μg/ml uPM10 for 8 weeks. Airway thickening and collagen accumulation were stained with H&E staining and Masson trichrome staining. The ROS production and mucus hypersecretion were examined with DHE staining, Alcian blue, periodic acid schiff staining and Western blotting. Bronchial epithelial BEAS-2B cells were treated 1–20 μM aesculetin, 20 μg/ml OxPAPC, and 1μM Erlotinib with 2 μg/ml uPM10 for 8 h or 48 h. The protein induction of TLR4, EGFR, and MUC5AC were measured. Results Exposure of mice to uPM10 enhanced total leukocyte number in the BALF with increase in neutrophils and lymphocytes, which was reversed by oral administration of 10 mg/kg aesculetin. In addition, aesculetin attenuated airway thickening along with collagen accumulation, mucus hypersecretion and ROS production elevated by uPM10 inhalation. Nontoxic aesculetin at the concentrations of 1–20 μM inhibited the induction of collagen proteins and MUC5AC in BEAS-2B cells promoted by 2 μg/ml uPM10. On the other hand, uPM10 accelerated the induction of TLR4 and EGFR in BEAS-2B cells, which dampened by 20 μM aesculetin. Both receptors inhibitor reduced the MUC5AC induction in BEAS-2B cells stimulated by uPM10. Conclusions These results demonstrate that aesculetin ameliorated airway thickening and mucus hypersecretion caused by uPM10 inhalation. Therefore, aesculetin maybe a promising agent treating progressive respiratory disorders elicited by urban microparticulates. Funding Sources This work was supported by the BK21 FOUR(Fostering Outstanding Universities for Research, 4220200913807) funded by the National Research Foundation of Korea (NRF).
doi:10.1093/cdn/nzab037_063 fatcat:33gj7scl4zgdbi4guzmsme6gju