Immune Modulation of Autoimmunity by Herbal Products

草药产品对自身免疫的免疫调节

• 批准号: 8103241
• 负责人: KAMAL D MOUDGIL
• 金额: $ 36.75万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8103241
• 关键词: Address; Adopted; Adoptive Transfer; Adult; Adverse reactions; Affect; American; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Antibody Formation; Antibody Suppression; Antigens; Antioxidants; Arthritis; Autoimmune Diseases; Autoimmune Responses; Autoimmunity; Botanicals; Celastraceae; Celastrus; Cell Migration Inhibition function; Cells; Centers for Disease Control and Prevention (U.S.); China; Chinese Herbs; Chronic; Clinical; Communities; Complementary and alternative medicine; Consumption; Diabetes Mellitus; Disease; Disease Outcome; Down-Regulation; Drug usage; Enhancing Antibodies; Experimental Models; Family; Folk Remedy; Frequencies; Gastrointestinal Diseases; Generations; Healthcare; Heat shock proteins; Herb; IL2RA gene; Immune; Immune response; Immune system; Immunosuppressive Agents; In Vitro; Infiltration; Inflammation Mediators; Inflammatory; Insulin-Dependent Diabetes Mellitus; Label; Lupus; Lymphocyte; Malignant Neoplasms; Mediating; Medicinal Herbs; Mind; Modality; Modeling; Mononuclear; Multiple Sclerosis; National Health Interview Survey; Nitric Oxide; Organ; Patients; Pattern; Pharmaceutical Preparations; Plant Roots; Plants; Process; Production; Property; Province; Publishing; Rattus; Regulatory T-Lymphocyte; Relative (related person); Rheumatism; Rheumatoid Arthritis; Serum; Severities; Stroke; Surveys; Systemic Lupus Erythematosus; T-Lymphocyte; T-Lymphocyte Epitopes; Testing; Therapeutic; Therapeutic Agents; Therapeutic Effect; Tissues; Toxic effect; Water; Western World; alternative treatment; base; cost; cytokine; design; feeding; human NOS2A protein; immunoregulation; in vivo; migration; mycobacterial; public health relevance; research study; response; stem; trafficking

DESCRIPTION (provided by applicant): At least 36 percent of adult Americans adopted some form of complementary and alternative medicine (CAM) therapy for their healthcare needs annually as surveyed 5 years ago (National Interview Health Survey of 2002, CDC). Among CAM modalities, the use of naturally grown plant products as efficacious therapeutic entities as well as the relative lack of toxicity of herbs compared to conventionally used drugs has popularized the consumption of botanical formulas in the western world. Despite the extensive use of medicinal herbs, the mechanisms of action remain unclear for most of them. Our preliminary study using an experimental model of autoimmunity has revealed that the Chinese herb Celastrus suppresses clinical disease and induces significant changes in antigen-specific immune response (e.g., deviation of the cytokine response from pro-inflammatory to anti-inflammatory type, and increased production of antigenspecific antibodies). In this study, we have proposed experiments to test the in-depth mechanisms of Celastrus-induced immune modulation operative via the CD4+CD25+ T regulatory cells (Treg), the in vivo trafficking of lymphocytes into the target organ, the protective antibodies, and the inflammatory mediators. In this respect, our proposal is an excellent match with the objectives of RFA-AT-08-003. Aim 1. To study the suppressive function of CD4+CD25+T cells that leads to the downregulation of the disease process in Celastrus-fed rats. Aim 2. To examine the mechanisms by which Celastrus reduces the migration of potentially pathogenic T cells into the target organ. Aim 3. To determine how enhanced antibody response to the disease-related antigen leads to suppression of the autoimmune response. Aim 4. To test for the Celastrus-induced modulation of inflammatory mediators in the target tissue. Although this proposal involves one CAM modality (a Chinese herb) and one experimental model of autoimmunity, we believe that the basic mechanistic principles elucidated in our study would also be applicable in part to other CAM modalities as well as other models of autoimmunity. Public Health Relevance: Natural plant products are increasingly being used by patients with a variety of autoimmune diseases, such as diabetes, multiple sclerosis, arthritis and lupus. However, the mechanisms of action of many of these products are not defined. We propose to study the immune system related mechanisms by which Celastrus, a Chinese herb, mediates its beneficial effects against autoimmunity. We will conduct these studies in an experimental model of autoimmunity. The results of our study would help developing rationally designed therapeutic approaches for autoimmunity using botanical products.

描述（由申请人提供）：根据5年前的调查，每年至少有36%的美国成年人采用某种形式的补充和替代医学（CAM）治疗来满足他们的医疗保健需求（2002年全国访谈健康调查，CDC）。在CAM模式中，使用天然生长的植物产品作为有效的治疗实体，以及与常规使用的药物相比草药相对缺乏毒性，已经在西方世界普及了植物配方的消费。尽管草药的广泛使用，但大多数草药的作用机制仍不清楚。我们使用自身免疫实验模型的初步研究表明，中草药南蛇藤可以抑制临床疾病并诱导抗原特异性免疫反应的显着变化（例如，细胞因子应答从促炎型向抗炎型的偏离，以及抗原特异性抗体的产生增加）。在这项研究中，我们提出了实验来测试南蛇藤诱导的免疫调节的深入机制，通过CD 4 + CD 25 + T调节细胞（Treg），在体内运输的淋巴细胞进入靶器官，保护性抗体，和炎症介质。在这方面，我们的建议与RFA-AT-08-003的目标非常匹配。目标1。目的研究CD 4 + CD 25 +T细胞的抑制功能，从而导致南蛇藤喂养大鼠疾病进程的下调。目标二。研究南蛇藤减少潜在致病性T细胞向靶器官迁移的机制。目标3.确定对疾病相关抗原的增强抗体应答如何导致自身免疫应答的抑制。目标4。检测南蛇藤对靶组织中炎症介质的诱导调节。虽然这一建议涉及一个CAM模式（中药）和一个实验模型的自身免疫，我们相信，在我们的研究中阐明的基本机理原则也将部分适用于其他CAM模式以及其他模型的自身免疫。 公共卫生相关性：天然植物产品越来越多地被患有各种自身免疫性疾病的患者使用，如糖尿病，多发性硬化症，关节炎和狼疮。然而，许多这些产品的作用机制尚未确定。本研究拟探讨中药南蛇藤抗自身免疫的免疫机制。我们将在自身免疫的实验模型中进行这些研究。我们的研究结果将有助于开发合理设计的治疗方法，使用植物产品的自身免疫。