The effect of quercetin on human neutrophil elastase-induced mucin5AC expression in human airway epithelial cells
The effect of quercetin on human neutrophil elastase-induced mucin5AC expression in human airway epithelial cells
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DOI：
10.1016/j.intimp.2012.07.008
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发表时间：
2012-10-01
影响因子：
5.6
通讯作者：
Perelman, Juliy M.
中科院分区：
文献类型：
--
作者：
Li, Na;Li, Qi;Perelman, Juliy M.
槲皮素是一种植物类黄酮，是一种有效的抗氧化剂和抗炎剂。粘液分泌过多是气道慢性炎症性疾病常见的病理改变。我们研究了槲皮素对人中性粒细胞弹性蛋白酶（HNE）诱导的气道上皮细胞粘蛋白5AC（MUC5AC）表达的影响及其分子机制。人气道上皮 (HBE16) 细胞用槲皮素预处理，并用 HNE 处理。我们发现，在仅用 HNE 处理的细胞中，HNE 诱导 MUC5AC 和 EGFR 水平显着增加。槲皮素以剂量依赖的方式抑制MUC5AC基因转录和蛋白表达，40μM起抑制作用显着。槲皮素预处理后，EGFR mRNA和蛋白表达显着下降。在三种MAPK蛋白中，只有磷酸化ERK1/2蛋白表达在单独使用HNE处理后显着增加，而在用槲皮素预处理后显着降低。 HNE 还激活磷酸化 PKC 蛋白的表达，该表达在用槲皮素预处理时减弱。这些结果表明槲皮素可以通过PKC/EGFR/ERK信号转导通路抑制FINE诱导的人气道上皮细胞中MUC5AC的表达。未来，槲皮素可能成为临床上治疗慢性炎症性气道疾病粘蛋白分泌过多的有价值的药物。 (C) 2012 Elsevier B.V. 保留所有权利。
Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. Mucus hypersecretion is a common pathological change in chronic inflammatory diseases of the airway. We investigated the effect of quercetin on mucin 5AC (MUC5AC) expression induced by human neutrophil elastase (HNE) in airway epithelial cells and its molecular mechanisms. Human airway epithelial (HBE16) cells were pretreated with quercetin and were treated with HNE. We found that HNE induced a significant increase in the levels of MUC5AC and EGFR in cells treated only with HNE. Quercetin suppressed gene transcription and protein expression of MUC5AC in a dose-dependent manner, with significant inhibition from 40 mu M. mRNA and protein expressions of EGFR decreased markedly when pretreated with quercetin. Among three MAPK proteins, only phosphorylated ERK1/2 protein expression increased significantly after treatment with HNE alone and decreased significantly after pretreatment with quercetin. HNE also activated phosphorylated PKC protein expression which was attenuated when pretreated with quercetin. These results suggest that quercetin can inhibit FINE-induced MUC5AC expression in human airway epithelial cells through PKC/EGFR/ERK signal transduction pathway. In the future, quercetin might be a valuable treatment for mucin hypersecretion in chronic inflammatory airway diseases in clinic. (C) 2012 Elsevier B.V. All rights reserved.