Department of Nutritional Medicine, University of Hohenheim, Fruwirthstraße 12, 70593 Stuttgart, Germany.
Department of Biochemistry and Molecular Biology, Institute for Medical Research-Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Int J Mol Sci. 2021 Jul 16;22(14):7640. doi: 10.3390/ijms22147640.
Mast cells play a critical role as main effector cells in allergic and other inflammatory diseases. Usage of anti-inflammatory nutraceuticals could be of interest for affected patients. Resveratrol, a natural polyphenol found in red grapes, is known for its positive properties. Here, we analyzed the effects of resveratrol on FcεRI-mediated activation of mature human mast cells isolated from intestinal tissue (hiMC). Resveratrol inhibited degranulation and expression of cytokines and chemokines such as CXCL8, CCL2, CCL3, CCL4, and TNF-α in a dose-dependent manner. Further, resveratrol inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and signal transducer and activator of transcription (STAT) 3. ERK1/2 is known to be involved in cytokine expression of hiMC and to directly interact with STAT3. Mitochondrial STAT3 is phosphorylated by ERK1/2 and contributes to mast cell degranulation. We were able to isolate mitochondrial fractions from small hiMC numbers and could show that activation of mitochondrial STAT3 and ERK1/2 in hiMC was also inhibited by resveratrol. Our results indicate that resveratrol inhibits hiMC activation by inhibiting the phosphorylation of mitochondrial and nuclear ERK1/2 and STAT3, and it could be considered as an anti-inflammatory nutraceutical in the treatment of mast cell-associated diseases.
肥大细胞作为过敏和其他炎症性疾病的主要效应细胞发挥着关键作用。使用抗炎性营养保健品可能对受影响的患者有益。白藜芦醇是一种存在于红葡萄中的天然多酚，具有积极的特性。在这里，我们分析了白藜芦醇对从肠道组织中分离的成熟人类肥大细胞（hiMC）FcεRI 介导的激活的影响。白藜芦醇以剂量依赖的方式抑制脱颗粒和细胞因子和趋化因子（如 CXCL8、CCL2、CCL3、CCL4 和 TNF-α）的表达。此外，白藜芦醇抑制细胞外信号调节激酶（ERK）1/2 和信号转导和转录激活因子（STAT）3 的磷酸化。ERK1/2 已知参与 hiMC 中细胞因子的表达，并与 STAT3 直接相互作用。线粒体 STAT3 被 ERK1/2 磷酸化，并有助于肥大细胞脱颗粒。我们能够从小量的 hiMC 中分离出线粒体部分，并能够表明线粒体 STAT3 和 ERK1/2 在 hiMC 中的激活也被白藜芦醇抑制。我们的结果表明，白藜芦醇通过抑制线粒体和核 ERK1/2 和 STAT3 的磷酸化来抑制 hiMC 的激活，它可以被认为是治疗肥大细胞相关疾病的抗炎性营养保健品。
