Hu Xin, Wang Jing, Xia Yu, Simayi Mihereguli, Ikramullah Syed, He Yuanbing, Cui Shihong, Li Shuang, Wushouer Qimanguli
Department of Respiratory Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
Department of Geriatrics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
Mol Med Rep. 2016 Dec;14(6):5231-5236. doi: 10.3892/mmr.2016.5884. Epub 2016 Oct 25.
Eosinophils exert a number of inflammatory effects through the degranulation and release of intracellular mediators, and are considered to be key effector cells in allergic disorders, including asthma. In order to investigate the regulatory effects of the natural polyphenol, resveratrol, on eosinophils derived from asthmatic individuals, the cell counting Kit‑8 assay and flow cytometry analysis were used to determine cell proliferation and cell cycle progression in these cells, respectively. Cellular apoptosis was detected using annexin V-fluorescein isothiocyanate/propidium iodide double‑staining. The protein expression levels of p53, p21, cyclin‑dependent kinase 2 (CDK2), cyclin A, cyclin E, Bim, B‑cell lymphoma (Bcl)‑2 and Bcl‑2‑associated X protein (Bax) were measured by western blot analysis following resveratrol treatment. The results indicated that resveratrol effectively suppressed the proliferation of eosinophils from asthmatic patients in a concentration‑ and time‑dependent manner. In addition, resveratrol was observed to arrest cell cycle progression in G1/S phase by increasing the protein expression levels of p53 and p21, and concurrently reducing the protein expression levels of CDK2, cyclin A and cyclin E. Furthermore, resveratrol treatment significantly induced apoptosis in eosinophils, likely through the upregulation of Bim and Bax protein expression levels and the downregulation of Bcl‑2 protein expression. These findings suggested that resveratrol may be a potential agent for the treatment of asthma by decreasing the number of eosinophils.
嗜酸性粒细胞通过脱颗粒和释放细胞内介质发挥多种炎症作用，被认为是包括哮喘在内的过敏性疾病中的关键效应细胞。为了研究天然多酚白藜芦醇对哮喘患者来源的嗜酸性粒细胞的调节作用，分别使用细胞计数试剂盒-8法和流式细胞术分析来测定这些细胞的增殖和细胞周期进程。采用膜联蛋白V-异硫氰酸荧光素/碘化丙啶双染法检测细胞凋亡。在白藜芦醇处理后，通过蛋白质印迹分析测定p53、p21、细胞周期蛋白依赖性激酶2（CDK2）、细胞周期蛋白A、细胞周期蛋白E、Bim、B细胞淋巴瘤（Bcl）-2和Bcl-2相关X蛋白（Bax）的蛋白表达水平。结果表明，白藜芦醇以浓度和时间依赖性方式有效抑制哮喘患者嗜酸性粒细胞的增殖。此外，观察到白藜芦醇通过增加p53和p21的蛋白表达水平，同时降低CDK2、细胞周期蛋白A和细胞周期蛋白E的蛋白表达水平，使细胞周期进程停滞在G1/S期。此外，白藜芦醇处理显著诱导嗜酸性粒细胞凋亡，可能是通过上调Bim和Bax蛋白表达水平以及下调Bcl-2蛋白表达。这些发现表明，白藜芦醇可能是一种通过减少嗜酸性粒细胞数量来治疗哮喘的潜在药物。
