Ginger Suppresses Phthalate Ester-Induced Airway Remodeling

摘要

This study has two novel findings: it is not only the first to demonstrate inflammatory cytokines, which are produced by the bronchial epithelium after exposure to phthalate esters and contribute to airway remodeling by increasing human bronchial smooth muscle cells (BSMC) migration and proliferation, but it is also the first to reveal that ginger reverses phthalate ester-mediated airway remodeling. Human bronchial epithelial cell lines BEAS-2B and HBE135-E6E7 (HBE) were treated with butylbenzyl phthalate (BBP), bis(2-ethylhexyl) phthalate (BEHP), dibutyl phthalate (DBP), and diethyl phthalate (DEP), and the conditioned medium (CM) was harvested and then added to BSMC. Cultures of BSMC with BBP-, BEHP-, DBP-, and DEP-BEAS-2B-CM and DEP-HBE-CM increased BSMC proliferation and migration, which are major features in asthma remodeling. Exposure of BEAS-2B and HBE to DBP caused epithelial cells to produce inflammatory cytokines IL-8 and RANTES, which subsequently induced BSMC proliferation and migration. Depleting both IL-8 and RANTES completely reversed the effect of DBP-BEAS-2B-CM and DBP-HBE-CM-mediated BSMC proliferation and migration, suggesting this effect is a synergistic influence of IL-8 and RANTES. Moreover, [6]-shogaol, [6]-gingerol, [8]-gingerol, and [l0]-gingerol, which are major bioactive compounds present in Zingiber officinale, suppress phthalate ester-mediated airway remodeling. This study suggests that ginger is capable of preventing phthalate ester-associated asthma.