Department of Physiology, Yeungnam University College of Medicine, Daegu, Korea.
Department of Otorhinolaryngology-Head and Neck Surgery, Yeungnam University College of Medicine, Daegu, Korea.
Clin Exp Otorhinolaryngol. 2013 Dec;6(4):237-42. doi: 10.3342/ceo.2013.6.4.237. Epub 2013 Nov 29.
Among the inflammatory mediators, phorbol 12-myristate 13-acetate (PMA) is associated with the regulation of MUC5B expression in the airway epithelial cells. Epigallocatechin-3-gallate (EGCG) is the major component of green tea extract. The biological activity of EGCG includes reduction of cholesterol and antioxidant activity, as well as anti-inflammatory effect. However, the precise action mechanism of anti-inflammatory effect of EGCG in the airway epithelial cells has not been fully defined. This study investigates the effect and the brief signaling pathway of EGCG on PMA-induced MUC5B expression in the airway epithelial cells.
In NCI-H292 airway epithelial cells, the effect and signaling pathway of EGCG on MUC5B expression were investigated using real-time polymerase chain reaction analysis, enzyme immunoassay, immunohistochemical analysis, gelatin zymography assay, and immunoblot analysis.
In NCI-H292 airway epithelial cells, PMA induced MUC5B expression, phosphorylation of p38 mitogen-activated protein kinase (MAPK), and matrix metalloproteinase-9 (MMP-9) expression and protein activity. EGCG significantly decreased PMA-induced MUC5B expression, phosphorylation of p38 MAPK, and MMP-9 expression and protein activity. SB203580 (p38 MAPK inhibitor) significantly decreased PMA-induced MMP-9 expression. In addition, SB203580 and MMP-9 I (MMP-9 inhibitor) significantly decreased PMA-induced MUC5B expression.
These results suggest that EGCG down-regulates PMA-induced MUC5B expression through the p38 MAPK dependent MMP-9 signaling pathway in human airway epithelial cells.
在炎症介质中,佛波醇 12-肉豆蔻酸 13-乙酸酯(PMA)与气道上皮细胞中 MUC5B 表达的调节有关。表没食子儿茶素没食子酸酯(EGCG)是绿茶提取物的主要成分。EGCG 的生物学活性包括降低胆固醇和抗氧化活性以及抗炎作用。然而,EGCG 在气道上皮细胞中的抗炎作用的确切作用机制尚未完全确定。本研究探讨了 EGCG 对气道上皮细胞中 PMA 诱导的 MUC5B 表达的影响及其简要信号通路。
在 NCI-H292 气道上皮细胞中,使用实时聚合酶链反应分析、酶免疫测定、免疫组织化学分析、明胶酶谱分析和免疫印迹分析研究了 EGCG 对 MUC5B 表达的影响及其信号通路。
在 NCI-H292 气道上皮细胞中,PMA 诱导 MUC5B 表达、p38 丝裂原活化蛋白激酶(MAPK)磷酸化和基质金属蛋白酶-9(MMP-9)表达和蛋白活性。EGCG 显著降低 PMA 诱导的 MUC5B 表达、p38 MAPK 磷酸化和 MMP-9 表达和蛋白活性。SB203580(p38 MAPK 抑制剂)显著降低 PMA 诱导的 MMP-9 表达。此外,SB203580 和 MMP-9 I(MMP-9 抑制剂)显著降低 PMA 诱导的 MUC5B 表达。
这些结果表明,EGCG 通过人气道上皮细胞中 p38 MAPK 依赖性 MMP-9 信号通路下调 PMA 诱导的 MUC5B 表达。