CAM Center for Epigenetic Regulation of Inflammation

CAM 炎症表观遗传调控中心

• 批准号: 9127094
• 负责人: Prakash S Nagarkatti
• 金额: $ 163.48万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9127094
• 关键词: Accounting; Acetylation; Address; Adverse effects; American; Anti-Inflammatory Agents; Anti-inflammatory; Area; Autoimmune Process; Ayurvedic Medicine; Bioinformatics; Botanicals; Cardiovascular system; Cells; China; Chronic; Clinical; Clinical Treatment; Colon; Colon Carcinoma; Complementary and alternative medicine; Complex; DNA; DNA Methylation; DNA Sequence; Data; Development; Dietary Indole; Disease; Disease model; Down-Regulation; Effector Cell; Ensure; Environmental Risk Factor; Epigenetic Process; Funding; Gene Expression; Genetic; Ginseng Preparation; Goals; Human Pathology; Immune; Immunologic Monitoring; India; Indoles; Inflammation; Inflammation Mediators; Inflammatory; Investigation; Laboratories; Lead; Liver; Mediating; Medicine; MicroRNAs; Modality; Modification; Molecular; Molecular Profiling; Myelogenous; Natural Products; Nerve Degeneration; Nutritional; Obesity; Pain; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Plants; Play; Prevention; Process; Property; Publications; Regulation; Research; Research Project Grants; Resveratrol; Role; Signal Pathway; Staging; Suppressor-Effector T-Lymphocytes; TLR2 gene; TLR4 gene; Testing; Translational Research; cancer type; chemical reaction; chromatin modification; effective therapy; epigenetic marker; epigenetic regulation; epigenome; gene function; genome-wide; histone methylation; innovation; neuroinflammation; novel; novel marker; public health relevance; receptor; response; specific biomarkers

DESCRIPTION (provided by applicant): This is a renewal application aimed at investigating the epigenetic pathways through which botanicals used commonly as CAM, suppress inflammation. During the previous funding cycle, we have made outstanding progress identifying novel cellular and molecular pathways through which botanicals mediate their anti- inflammatory properties. Inflammation can trigger a wide range of diseases including autoimmune, cardiovascular, neurodegenerative, obesity, and certain types of cancer. For this reason, it is not only critical to uncover as-yet-unknown immune mechanisms and mediators of inflammation but also find novel treatment modalities. Because currently there are no medications that can effectively treat chronic inflammation and associated pain without significant side effects, our proposed studies are highly significant. Traditionally, the medicine practiced in India (Ayurveda) and China have used herbal products to treat inflammatory disorders. Also, more than 25% of the pharmaceuticals are derived from plants, which suggests that botanicals offer novel modalities against inflammation. Epigenetic modifications of chromatin and DNA have been shown recently to play a critical role in the regulation in human pathologies, including inflammation. Thus, the concept that botanicals used as CAM may mediate their effects through epigenetic regulation is highly innovative. The primary objective of the Center is to test the overarching hypothesis that botanicals currently used as CAM, regulate the epigenetic signaling pathways through interactions with specific receptors on immune cells to modulate gene expression leading to amelioration of inflammation. This will be tested using four research projects, 1) Identifying epigenetic pathways through which resveratrol (RES) triggers myeloid- derived suppressor cells (MDSCs) in the regulation of neuroinflammation. 2) Epigenetic regulation of Nrf2 signaling pathway in American ginseng (AG)-mediated suppression of inflammation in the colon and colon cancer. 3) Elucidation of the epigenetic mechanisms underlying dietary indole-mediated amelioration of inflammation in the colon specifically addressing how indoles activate AhR to promote Tregs and suppress Th17 cells. 4) Identifying the role of Sparstolonin B (a compound isolated from Sparganium stoloniferum tubers), as a TLR2 and TLR4 antagonist, thereby suppressing inflammation in the liver through epigenetic regulation. The projects are highly integrated and synergistic, all addressing epigenetic pathways so that the data generated from one project will benefit other projects. The projects will use an Administrative Core which will coordinate all activities of the Center and ensure scientific and programmatic progress. All projects will also use an Analytical Core which will perform genome-wide DNA methylation, histone methylation/acetylation, microRNA arrays, immune monitoring, bioinformatics and natural product integrity testing. Together, our CAM Center will identify epigenetic biomarkers and pathways through which botanicals suppress inflammation thereby paving the way for better treatment modality against inflammatory diseases.

描述（由申请人提供）：这是一种续签应用，旨在调查植物体通常用作CAM的表观遗传途径，从而抑制炎症。在上一个融资周期中，我们取得了出色的进步，鉴定了新型的细胞和分子途径，植物会通过这些途径介导其抗炎性特性。炎症会引发多种疾病，包括自身免疫，心血管，神经退行性，肥胖和某些类型的癌症。因此，不仅要揭示尚未尚未尚未尚未炎症的免疫机制和炎症介质，而且还发现了新的治疗方式。由于目前没有药物可以有效地治疗慢性炎症和相关的疼痛而没有明显的副作用，因此我们的拟议研究非常重要。传统上，印度（阿育吠陀）和中国实践的药物使用草药来治疗炎症疾病。同样，超过25％的药物来自植物，这表明植物会提供针对炎症的新型方式。最近已显示染色质和DNA的表观遗传修饰在包括炎症在内的人类病理中起关键作用。因此，用作CAM的植物体可以通过表观遗传调节介导其作用的概念具有很高的创新性。该中心的主要目的是检验植物当前用作CAM的总体假设，通过与免疫细胞上的特定受体相互作用来调节表观遗传信号通路，以调节基因表达，从而改善炎症的改善。这将使用四个研究项目进行测试，1）识别白藜芦醇（RES）通过这些途径触发髓样衍生的抑制细胞（MDSC）在神经炎症的调节中。 2）美国人参（AG）介导的结肠癌和结肠癌抑制炎症的NRF2信号通路的表观遗传调节。 3）阐明了饮食吲哚介导的结肠炎症改善的表观遗传机制，专门针对吲哚如何激活AHR以促进Tregs和抑制Th17细胞。 4）确定尖舌蛋白B（从斯替洛烯纤维块茎中分离出的化合物）作为TLR2和TLR4拮抗剂，从而通过表观遗传调节抑制肝脏的炎症。这些项目是高度融合和协同作用的，所有项目都涉及表观遗传途径，因此从一个项目产生的数据将使其他项目受益。这些项目将使用管理核心，该核心将协调中心的所有活动，并确保科学和程序化的进步。所有项目还将使用分析核心，该核心将执行全基因组DNA甲基化，组蛋白甲基化/乙酰化，microRNA阵列，免疫监测，生物信息学和自然产物完整性测试。我们的凸轮中心将共同确定植物学抑制炎症的表观遗传生物标志物和途径，从而为针对炎症性疾病更好的治疗方式铺平了道路。