Impact of phytochemicals on epigenetic regulation of cytokine gene expression and immune cell function

植物化学物质对细胞因子基因表达和免疫细胞功能的表观遗传调控的影响

• 批准号: RGPIN-2017-05339
• 负责人: Hoskin, David
• 金额: $ 2.04万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629792
• 关键词: Impact; phytochemicals; epigenetic; regulation; cytokine

The immune system is responsible for defending against infection by disease-causing microorganisms and eliminating spontaneously-arising cancer cells; however, inappropriate activation of the immune system can lead to potentially harmful uncontrolled inflammation. Interestingly, fruits, vegetables, spices, and some beverages contain a number of potent inflammation-inhibiting substances belonging to a family of plant-derived chemicals known as dietary phytochemicals or phytonutrients. Diets that are rich in phytochemicals are believed to reduce potentially harmful inflammatory responses, at least in part by reducing the production of inflammation-inducing chemical messengers known as cytokines by various cells of the immune system. The mechanism(s) by which these dietary phytochemicals regulate inflammation-promoting cytokine production are not well understood. On the basis of recent evidence that certain dietary phytochemicals are able to modify DNA and thereby regulate the expression of cancer cell genes, we propose that the same epigenetic processes allow certain phytochemicals and/or their major metabolites to control cytokine production by immune cells. Mice are commonly used as a source of immune cells with which to study the molecular basis of processes involved in human immune cell function. We will therefore use a mouse model system to determine the effect of a panel of representative phytonutrients and their major metabolites on the expression and activation of DNA-modifying enzymes in cytokine-producing cells of the innate immune system (macrophages, dendritic cells) and adaptive immune system (T cells). We anticipate that our results will demonstrate a causal effect on inflammation-promoting and inflammation-inhibiting cytokine synthesis by these immune cells. This fundamental immunology research will yield new information on the potential impact of a phytochemical-rich diet on innate and adaptive immune cell function, and inform future studies on the impact of dietary phytochemicals and their major metabolites on immune cell function in vitro and in vivo.

免疫系统负责防御致病微生物的感染并消除自发产生的癌细胞;然而，免疫系统的不适当激活可能导致潜在有害的不受控制的炎症。有趣的是，水果、蔬菜、香料和一些饮料含有许多有效的炎症抑制物质，这些物质属于植物衍生的化学物质家族，称为膳食植物化学物质或植物营养素。富含植物化学物质的饮食被认为可以减少潜在的有害炎症反应，至少部分是通过减少免疫系统各种细胞产生的炎症诱导化学信使（称为细胞因子）。这些膳食植物化学物质调节促炎细胞因子产生的机制尚不清楚。最近的证据表明，某些膳食植物化学物质能够修饰DNA，从而调节癌细胞基因的表达的基础上，我们提出，相同的表观遗传过程允许某些植物化学物质和/或其主要代谢产物，以控制免疫细胞的细胞因子的产生。小鼠通常被用作免疫细胞的来源，用于研究参与人类免疫细胞功能的过程的分子基础。因此，我们将使用小鼠模型系统来确定一组代表性植物营养素及其主要代谢产物对先天免疫系统（巨噬细胞、树突细胞）和适应性免疫系统（T细胞）的产精氨酸细胞中DNA修饰酶的表达和活化的影响。我们预计，我们的研究结果将证明这些免疫细胞对炎症促进和炎症抑制细胞因子合成的因果关系。这项基础免疫学研究将产生关于富含植物化学物质的饮食对先天性和适应性免疫细胞功能的潜在影响的新信息，并为未来关于饮食植物化学物质及其主要代谢产物对免疫细胞功能的影响的研究提供信息。