韧皮部
支气管肺泡灌洗
炎症
化学
粘液
肿瘤坏死因子α
粘蛋白
细胞因子
MAPK/ERK通路
体内
免疫学
药理学
肺
医学
内科学
生物
激酶
生物化学
生物技术
生态学
作者
Hao Wang,Ting Yang,Tao Wang,Nanya Hao,Yongchun Shen,Yanqiu Wu,Zhicheng Yuan,Lei Chen,Fuqiang Wen
标识
DOI:10.1016/j.intimp.2017.12.009
摘要
Cigarette smoke (CS)-induced airway mucus hypersecretion and inflammation are the prominent features of chronic obstructive pulmonary disease (COPD). As an anti-inflammatory flavonoid, phloretin was found to be involved in various inflammatory disorders such as sepsis. In this study, the effects of phloretin on CS-induced airway mucin secretion and inflammation were investigated in vivo and in vitro.Phloretin dissolved in 1% DMSO was daily injected intraperitoneally to mice, which were then exposed to CS for four weeks. Mouse lung histologic changes were evaluated, the expression of mucin 5ac (MUC5AC) was measured, bronchoalveolar lavage fluid (BALF) total cells, neutrophils, and macrophages were counted. BALF and lung levels of tumor necrosis factor-alpha and interleukin-1 beta (IL-1β) were quantified. Moreover, the effects of phloretin on cigarette smoke extract (CSE)-induced expression of MUC5AC and IL-1β were investigated in NCI-H292 cells. Then, to explore the potential mechanisms, the signaling molecules including epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK) and P38 were evaluated.Phloretin pretreatment dramatically suppressed the mucins secretion, inflammatory cell infiltration and inflammatory cytokine release in mouse lungs induced by CS, and it also suppressed CSE-induced expression of MUC5AC and IL-1β in NCI-H292 bronchial epithelial cells. Furthermore, western blot showed that phloretin attenuated the activation of EGFR, ERK and P38 both in vivo and in vitro.This study highlights the protective effect of phloretin on CS-related airway mucus hypersecretion and inflammation, where EGFR, ERK and P38 might be involved. These findings suggest that phloretin could be a potential therapeutic drug for COPD.
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