Kim Hyun Jik, Park Sang Ho, Park Sung-Yoon, Moon Uk Yeol, Lee Byung Don, Yoon Sung Hyun, Lee Jeung-Gweon, Baek Seung Joon, Yoon Joo-Heon
Department of Otolaryngology-Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University, Seoul, Korea.
J Nutr Biochem. 2008 Aug;19(8):536-544. doi: 10.1016/j.jnutbio.2007.06.010. Epub 2007 Dec 21.
It has been reported that the proinflammatory cytokine interleukin-1beta (IL-1beta) induces mucus hypersecretion in normal human nasal epithelial (NHNE) cells and that the MAP kinase pathway may be an important signal pathway in IL-1beta-induced MUC5AC gene expression. Green tea (Camellia sinensis) polyphenols are potent anti-inflammatory agents and have been shown to inhibit inflammation in tumor cell lines and cultured respiratory epithelial cells. In this study, we examined the effect of (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, on IL-1beta-induced MUC5AC gene expression and secretion in NHNE cells. After cells had been treated with IL-1beta (10 ng/ml) and pretreated with EGCG (10, 50 and 100 microM), mRNA expression of MUC5AC was determined by real-time polymerase chain reaction. The suppression of each signal pathway protein was determined by Western blot analysis after treatment with IL-1beta and EGCG, respectively. IL-1beta increased MUC5AC gene expression and MUC5AC secretion. EGCG markedly suppressed IL-1beta-induced MUC5AC gene expression and MUC5AC secretion via suppression of the phosphorylation of ERK MAP kinase, MSK1, and transcription factor, cAMP response element-binding protein. IL-1beta increased the number of cells staining positive with MUC5AC antibodies, and EGCG treatment decreased this number. Our data suggest that EGCG may be an effective inhibitor of IL-1beta-induced mucus hypersecretion.
据报道，促炎细胞因子白细胞介素 -1β（IL -1β）可诱导正常人鼻上皮（NHNE）细胞黏液分泌过多，且丝裂原活化蛋白激酶（MAP）激酶途径可能是IL -1β诱导MUC5AC基因表达的重要信号途径。绿茶（茶树）多酚是强效抗炎剂，已被证明可抑制肿瘤细胞系和培养的呼吸道上皮细胞中的炎症。在本研究中，我们检测了绿茶多酚（-）-表没食子儿茶素 -3 -没食子酸酯（EGCG）对IL -1β诱导的NHNE细胞中MUC5AC基因表达和分泌的影响。在用IL -1β（10 ng/ml）处理细胞并分别用EGCG（10、50和100 microM）预处理后，通过实时聚合酶链反应测定MUC5AC的mRNA表达。在用IL -1β和EGCG处理后，通过蛋白质印迹分析分别测定各信号通路蛋白的抑制情况。IL -1β增加了MUC5AC基因表达和MUC5AC分泌。EGCG通过抑制细胞外信号调节激酶（ERK）MAP激酶、丝裂原和应激激活蛋白激酶1（MSK1）以及转录因子环磷酸腺苷反应元件结合蛋白（cAMP response element-binding protein，CREB）的磷酸化，显著抑制了IL -1β诱导的MUC5AC基因表达和MUC5AC分泌。IL -1β增加了MUC5AC抗体染色阳性的细胞数量，而EGCG处理减少了这一数量。我们的数据表明，EGCG可能是IL -1β诱导的黏液分泌过多的有效抑制剂。
