School of Chinese Medicine, The University of Hong Kong, 1/F, Estate Building, 10 Sassoon Road, Pokfulam, Hong Kong, China.
Inflamm Res. 2013 Mar;62(3):313-24. doi: 10.1007/s00011-012-0584-x. Epub 2012 Dec 25.
Our previous study demonstrated that polysaccharides of Dendrobium officinale Kimura et Migo (DP) were capable of enhancing immunomodulation in an experimental model of Sjögren's syndrome, a chronic autoimmune disease mainly affecting the salivary glands. In the present study, we further investigated the protective effect of DP on a human salivary gland cell line A-253 against tumor necrosis factor (TNF)-α-induced apoptosis.
TNF-α (100 U/ml) was used as the stimulus for treating the A-253 cells to induce cellular apoptosis. Nuclear factor-kappa B (NF-κB, p65), phosphorylation of mitogen-activated protein kinases (MAPK), reactive oxygen species (ROS) generation, mitochondrial membrane potential and proapoptotic proteins were examined. A-253 cells were pre-treated with DP for 12 h before TNF-α stimulation.
We observed translocation of NF-κB into the nuclei, prolonged MAPK, excessive ROS generation and strongly decreased mitochondrial membrane potential, and subsequently cytochrome C release and caspase-3 activation. However, pre-treatment with DP significantly inhibited the TNF-α-induced apoptotic factors.
Our data suggested the inhibitory effect of DP on TNF-α-induced apoptosis in a human salivary gland cell line. This inhibition indicated potential inference of DP in the initial plasma membrane-bound complex of TNF-α and its receptors.
我们之前的研究表明,铁皮石斛多糖(DP)能够增强干燥综合征(一种主要影响唾液腺的慢性自身免疫性疾病)实验模型中的免疫调节作用。在本研究中,我们进一步研究了 DP 对人唾液腺细胞系 A-253 抵抗肿瘤坏死因子(TNF)-α诱导的细胞凋亡的保护作用。
将 TNF-α(100 U/ml)用作刺激物来处理 A-253 细胞以诱导细胞凋亡。检测核因子-κB(NF-κB,p65)、丝裂原活化蛋白激酶(MAPK)磷酸化、活性氧(ROS)生成、线粒体膜电位和促凋亡蛋白。在 TNF-α刺激前,用 DP 预处理 A-253 细胞 12 小时。
我们观察到 NF-κB 向细胞核内易位、MAPK 延长、ROS 过度生成和线粒体膜电位明显下降,随后细胞色素 C 释放和 caspase-3 激活。然而,DP 的预处理显著抑制了 TNF-α诱导的凋亡因子。
我们的数据表明 DP 对人唾液腺细胞系中 TNF-α诱导的细胞凋亡具有抑制作用。这种抑制作用表明 DP 可能参与了 TNF-α与其受体在初始质膜结合复合物中的相互作用。