Loss of E-cadherin due to road dust PM2.5 activates the EGFR in human pharyngeal epithelial cells

Tung, Nguyen Thanh; Ho, Kin-Fai; Niu, Xinyi; Sun, Jian; Shen, Zhenxing; Wu, Feng; Cao, Junji; Dung, Hoang Ba; Thuy, Tran Phan Chung; Hsiao, Ta-Chih; Liu, Wen-Te; Chuang, Hsiao-Chi

Loss of E-cadherin due to road dust PM2.5 activates the EGFR in human pharyngeal epithelial cells

2021

Exposure to road dust particulate matter (PM) causes adverse health impacts on the human airway. However, the effects of road dust on the upper airway epithelium in humans remain unclear. We investigated the involvement of the epidermal growth factor receptor (EGFR) after PM with an aerodynamic diameter of < 2.5 μm (PM₂.₅)-induced E-cadherin disruption of human pharyngeal epithelial cells. First, we collected road dust PM₂.₅ from 10 Chinese cities, including Wuhan, Nanjing, Shanghai, Guangzhou, Chengdu, Beijing, Lanzhou, Tianjin, Harbin, and Xi’an. Human pharyngeal FaDu cells were exposed to road dust PM₂.₅ at 50 μg/mL for 24 h, cytotoxicity (cell viability and lactate dehydrogenase (LDH)) was assessed, and expressions of the proinflammatory interleukin (IL)-6 and high-mobility group box 1 (HMGB1) protein, receptor for advanced glycation end products (RAGE), occludin, E-cadherin, EGFR, and phosphorylated (p)-EGFR were determined. The E-cadherin gene was then knocked down to investigate EGFR activation in FaDu cells. Exposure to road dust PM₂.₅ resulted in a decrease in cell viability and increases in LDH and IL-6. Our data suggested that PM₂.₅ could decrease expressions of occludin and E-cadherin and increase expressions of EGFR and p-EGFR, which was confirmed by E-cadherin-knockdown. Our results showed a negative association between the alterations in E-cadherin and total elemental components in correlation analysis, especially S, Cl, K, Ti, Mn, Fe, Cu, Zn, and Pb. Exposure to metals in PM₂.₅ from road dust may lead to loss of the barrier function of the upper airway epithelium and activation of the EGFR. Our study showed the adverse effects of road dust PM₂.₅ on pharyngeal epithelial cells of the human upper airway.

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