Department of Medical Biology, School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, P.R. China.
Mol Med Rep. 2020 Mar;21(3):1658-1666. doi: 10.3892/mmr.2020.10952. Epub 2020 Jan 20.
Resveratrol (RSV), a natural polyphenol found in grapes and other herbal plants, has been reported to possess anti‑inflammatory, anti‑oxidative and anti‑proliferative activities. The aim of the present study was to investigate the effect of RSV on interleukin (IL)‑33‑induced inflammatory responses in mast cells and identify the underlying molecular mechanisms. Rat basophilic leukemia (RBL‑2H3) cells were stimulated with IL‑33 in the presence or absence of RSV. MTT, ELISA, reverse transcription‑quantitative PCR and western blot analyses were then performed in order to assess cytotoxicity, inflammatory cytokine production, suppression of tumorigenicity 2 receptor expression, protein expression involved in mitogen‑activated protein kinase (MAPK) and nuclear factor (NF)‑κB signaling, respectively. Finally, rats were used to determine the biological effect of RSV in vivo. The results revealed that RSV inhibited cell viability and increased cytotoxicity in a dose‑dependent manner. Medium concentration of RSV (10 µM) treatment attenuated inflammatory cytokine production, such as IL‑6, IL‑13, tumor necrosis factor‑α and monocyte chemotactic protein‑1, and curbed IL‑33‑induced enhancement of immunoglobulin E‑mediated responses in RBL‑2H3 cells, which were associated with the suppression of NF‑κB‑mediated transcription and inhibition of P38 phosphorylation in response to IL‑33 stimulation, but not extracellular signal regulated kinase or JNK. Notably, RSV application also decreased the levels of inflammatory cytokines in rats induced by IL‑33 injection, which was similar to the anti‑inflammatory effect in vitro. The data from the present study demonstrated that RSV played a regulatory role in antagonizing the effects of IL‑33 on mast cells both in vitro and in vivo, suggesting that it has therapeutic potential in IL‑33‑mediated inflammatory diseases that are associated with mast cells.
白藜芦醇（RSV）是一种天然多酚，存在于葡萄和其他草药植物中，已被报道具有抗炎、抗氧化和抗增殖活性。本研究旨在探讨 RSV 对肥大细胞中白细胞介素（IL）-33 诱导的炎症反应的影响，并确定其潜在的分子机制。用 IL-33 刺激大鼠嗜碱性白血病（RBL-2H3）细胞，同时存在或不存在 RSV。然后进行 MTT、ELISA、逆转录定量 PCR 和 Western blot 分析，以分别评估细胞毒性、炎症细胞因子产生、肿瘤坏死因子 2 受体表达抑制、丝裂原活化蛋白激酶（MAPK）和核因子（NF）-κB 信号转导相关蛋白表达。最后，使用大鼠确定 RSV 在体内的生物学效应。结果表明，RSV 呈剂量依赖性抑制细胞活力并增加细胞毒性。中浓度 RSV（10 μM）处理可减弱炎症细胞因子的产生，如 IL-6、IL-13、肿瘤坏死因子-α和单核细胞趋化蛋白-1，并抑制 IL-33 诱导的 RBL-2H3 细胞中免疫球蛋白 E 介导的反应增强，这与 NF-κB 介导的转录抑制和 IL-33 刺激时 P38 磷酸化抑制有关，但与细胞外信号调节激酶或 JNK 无关。值得注意的是，RSV 应用还降低了 IL-33 注射诱导的大鼠炎症细胞因子水平，这与体外抗炎作用相似。本研究的数据表明，RSV 在体外和体内均对肥大细胞中 IL-33 的作用发挥调节作用，表明其在与肥大细胞相关的 IL-33 介导的炎症性疾病中具有治疗潜力。
