Receptor activator of NF-κB ligand (RANKL) as an osteoclast differentiation factor induces inflammatory reactions via production of thymic stromal lymphopoietin (TSLP). Epigallocatechin gallate (EGCG) is the major and the most active compound in green tea and has anti-inflammatory, anti-cancer, anti-oxidant, and neuroprotective effects. However, the effect and molecular mechanisms of EGCG are still unknown in RANKL-induced inflammatory reactions. Here we investigated the immuno-regulatory effects and its molecular mechanisms of epigallocatechin gallate (EGCG) in RANKL-stimulated human mast cell line, HMC-1 cells. In this study, EGCG prevented expression of PI3 Kinase and phosphorylation of mitogen-activated protein (MAP) Kinases in RANKL-stimulated HMC-1 cells. EGCG prevented caspase-1 activity and decreased transcriptional activity of nuclear factor (NF)-κB by suppressing inhibitory protein κBα phosphorylation in RANKL-stimulated HMC-1 cells. EGCG has been shown to prevent production and mRNA expression of TSLP, interleukin (IL)-1β, IL-6, and IL-8 by RANKL without cytotoxicity. Furthermore, EGCG prevented degranulation of mast cell in RANKL-stimulated HMC-1 cells. Overall, these results suggest that EGCG acts as a natural agent for preventing and treating RANKL-mediated inflammatory diseases by targeting PI3 Kinase, MAP Kinase, caspase-1, and NF-κB signaling cascade in mast cells.

作为破骨细胞分化因子的NF-κB配体（RANKL）受体激活剂通过产生胸腺基质淋巴细胞生成素（TSLP）诱导炎症反应。表没食子儿茶素没食子酸酯（EGCG）是绿茶中主要和最活跃的化合物，具有抗炎，抗癌，抗氧化和神经保护作用。但是，EGCG的作用和分子机制在RANKL诱导的炎症反应中仍然未知。在这里，我们研究了表没食子儿茶素没食子酸酯（EGCG）在RANKL刺激的人类肥大细胞系HMC-1细胞中的免疫调节作用及其分子机制。在这项研究中，EGCG阻止了RANKL刺激的HMC-1细胞中PI3激酶的表达和有丝分裂原活化蛋白（MAP）激酶的磷酸化。EGCG通过抑制RANKL刺激的HMC-1细胞中的抑制性蛋白κBα磷酸化，从而阻止了caspase-1活性并降低了核因子（NF）-κB的转录活性。EGCG已显示可通过RANKL阻止TSLP，白介素（IL）-1β，IL-6和IL-8的产生和mRNA表达而无细胞毒性。此外，EGCG可防止RANKL刺激的HMC-1细胞中肥大细胞脱粒。总体而言，这些结果表明，EGCG通过靶向肥大细胞中的PI3激酶，MAP激酶，caspase-1和NF-κB信号传导级联，充当预防和治疗RANKL介导的炎性疾病的天然药物。和RANKL的IL-8没有细胞毒性。此外，EGCG可防止RANKL刺激的HMC-1细胞中肥大细胞脱粒。总体而言，这些结果表明，EGCG通过靶向肥大细胞中的PI3激酶，MAP激酶，caspase-1和NF-κB信号传导级联，充当预防和治疗RANKL介导的炎性疾病的天然药物。和RANKL的IL-8没有细胞毒性。此外，EGCG可防止RANKL刺激的HMC-1细胞中肥大细胞脱粒。总体而言，这些结果表明，EGCG通过靶向肥大细胞中的PI3激酶，MAP激酶，caspase-1和NF-κB信号传导级联，充当预防和治疗RANKL介导的炎性疾病的天然药物。