Blockade of eosinophil-induced bronchial epithelial-mesenchymal transition with a geranyl acetophenone in a coculture model

• Main Authors: Lee, Yu Zhao, Yap, Hui Min, Shaari, Khozirah, Tham, Chau Ling, Sulaiman, Mohd Roslan, Israf Ali, Daud Ahmad
• Format: Article
• Language: English
• Published: Frontiers Research Foundation 2017
• Online Access: http://psasir.upm.edu.my/id/eprint/61018/1/Blockade%20of%20eosinophil-induced%20bronchial%20epithelial-mesenchymal%20transition%20with%20a%20geranyl%20acetophenone%20in%20a%20coculture%20model.pdf; http://psasir.upm.edu.my/id/eprint/61018/; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696322/pdf/fphar-08-00837.pdf

Epithelial-mesenchymal transition (EMT) is currently recognized as the main cellular event that contributes to airway remodeling. Eosinophils can induce EMT in airway epithelial cells via increased transforming growth factor (TGF)-β production. We assessed the effect of synthetic 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA) upon eosinophil-induced EMT in a cellular model. The human eosinophil cell line EoL-1 was used to induce EMT in BEAS-2B human bronchial epithelial cells. The induction of EMT was dose-dependently suppressed following tHGA treatment in which the epithelial morphology and E-cadherin expression were not altered. Protein and mRNA expression of vimentin, collagen I and fibronectin in eosinophil-induced epithelial cells were also significantly suppressed by tHGA treatment. Following pathway analysis, we showed that tHGA suppressed eosinophil-induced activator protein-1-mediated TGF-β production by targeting c-Jun N-terminal kinase and phosphoinositide 3-kinase signaling pathways. These findings corroborated previous findings on the ability of tHGA to inhibit experimental murine airway remodeling.