Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, No. 100 Shih-Chuan first Road, Kaohsiung 807, Taiwan.
J Agric Food Chem. 2011 Apr 13;59(7):3429-38. doi: 10.1021/jf1049485. Epub 2011 Mar 14.
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 [10]-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.
这不仅是首次证明了邻苯二甲酸酯暴露于支气管上皮细胞后产生的炎症细胞因子通过增加人支气管平滑肌细胞(BSMC)迁移和增殖来促进气道重塑,而且还首次揭示了生姜逆转邻苯二甲酸酯介导的气道重塑。用人支气管上皮细胞系 BEAS-2B 和 HBE135-E6E7(HBE)用丁基苄基邻苯二甲酸酯(BBP)、双(2-乙基己基)邻苯二甲酸酯(BEHP)、邻苯二甲酸二丁酯(DBP)和邻苯二甲酸二乙酯(DEP)处理,然后收获条件培养基(CM)并添加到 BSMC 中。用 BBP、BEHP、DBP 和 DEP-BEAS-2B-CM 和 DEP-HBE-CM 处理的 BSMC 培养物增加了 BSMC 的增殖和迁移,这是哮喘重塑的主要特征。BEAS-2B 和 HBE 暴露于 DBP 导致上皮细胞产生炎症细胞因子 IL-8 和 RANTES,随后诱导 BSMC 增殖和迁移。耗尽 IL-8 和 RANTES 可完全逆转 DBP-BEAS-2B-CM 和 DBP-HBE-CM 介导的 BSMC 增殖和迁移的作用,表明这种作用是 IL-8 和 RANTES 的协同影响。此外,姜中的主要生物活性化合物[6]-姜酚、[6]-姜烯酚、[8]-姜酚和[10]-姜酚抑制邻苯二甲酸酯介导的气道重塑。这项研究表明,生姜能够预防邻苯二甲酸酯相关的哮喘。