Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Int Immunopharmacol. 2012 Oct;14(2):195-201. doi: 10.1016/j.intimp.2012.07.008. Epub 2012 Jul 21.
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 μM. 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 HNE-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.
槲皮素是一种植物类黄酮,具有很强的抗氧化和抗炎作用。黏液高分泌是气道慢性炎症性疾病的一种常见病理改变。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黏蛋白 5AC(MUC5AC)表达的影响及其分子机制。用槲皮素预处理人气道上皮(HBE16)细胞,并用 HNE 处理。我们发现,仅用 HNE 处理的细胞中 MUC5AC 和 EGFR 的水平显著增加。槲皮素呈剂量依赖性抑制 MUC5AC 的基因转录和蛋白表达,40μM 时抑制作用显著。用槲皮素预处理后,EGFR 的 mRNA 和蛋白表达明显下降。在三种 MAPK 蛋白中,只有磷酸化 ERK1/2 蛋白表达在单独用 HNE 处理后显著增加,在用槲皮素预处理后显著降低。HNE 还激活了磷酸化 PKC 蛋白的表达,而用槲皮素预处理则减弱了其表达。这些结果表明,槲皮素可通过 PKC/EGFR/ERK 信号转导通路抑制 HNE 诱导的人气道上皮细胞 MUC5AC 表达。在未来,槲皮素可能成为治疗慢性炎症性气道疾病中黏液高分泌的一种有价值的药物。