Zingg Jean-Marc
Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland.
Vitam Horm. 2007;76:393-418. doi: 10.1016/S0083-6729(07)76015-6.
Mast cells play an important role in the immune system by interacting with B and T cells and by releasing several mediators involved in activating other cells. Hyperreactivity of mast cells and their uncontrolled accumulation in tissues lead to increased release of inflammatory mediators contributing to the pathogenesis of several diseases such as rheumatoid arthritis, atherosclerosis, multiple sclerosis, and allergic disorders such as asthma and allergic rhinitis. Interference with mast cell proliferation, survival, degranulation, and migration by synthetic or natural compounds may represent a preventive strategy for the management of these diseases. Natural vitamin E covers a group of eight analogues-the alpha-, beta-, gamma-, and delta-tocopherols and the alpha-, beta-, gamma-, and delta-tocotrienols, but only alpha-tocopherol is efficiently retained by the liver and distributed to peripheral tissues. Mast cells preferentially locate in the proximity of tissues that interface with the external environment (the epithelial surface of the skin, the gastrointestinal mucosa, and the respiratory system), what may render them accessible to treatments with inefficiently retained natural vitamin E analogues and synthetic derivatives. In addition to scavenging free radicals, the natural vitamin E analogues differently modulate signal transduction and gene expression in several cell lines; in mast cells, protein kinase C, protein phosphatase 2A, and protein kinase B are affected by vitamin E, leading to the modulation of proliferation, apoptosis, secretion, and migration. In this chapter, the possibility that vitamin E can prevent diseases with mast cells involvement by modulating signal transduction and gene expression is evaluated.
肥大细胞通过与B细胞和T细胞相互作用以及释放多种参与激活其他细胞的介质,在免疫系统中发挥重要作用。肥大细胞的高反应性及其在组织中的不受控制的积累导致炎症介质释放增加,这促成了几种疾病的发病机制,如类风湿性关节炎、动脉粥样硬化、多发性硬化症,以及哮喘和过敏性鼻炎等过敏性疾病。合成或天然化合物对肥大细胞增殖、存活、脱颗粒和迁移的干扰可能代表了管理这些疾病的一种预防策略。天然维生素E包括一组八种类似物——α-、β-、γ-和δ-生育酚以及α-、β-、γ-和δ-生育三烯酚,但只有α-生育酚能被肝脏有效保留并分布到外周组织。肥大细胞优先位于与外部环境接触的组织附近(皮肤的上皮表面、胃肠道黏膜和呼吸系统),这可能使它们易于接受低效保留的天然维生素E类似物和合成衍生物的治疗。除了清除自由基外,天然维生素E类似物在几种细胞系中对信号转导和基因表达有不同的调节作用;在肥大细胞中,蛋白激酶C、蛋白磷酸酶2A和蛋白激酶B受维生素E影响,导致增殖、凋亡、分泌和迁移的调节。在本章中,评估了维生素E通过调节信号转导和基因表达预防肥大细胞参与的疾病的可能性。