THYROCYTES EXPRESS INFLAMMATORY MEDIATORS

甲状腺细胞表达炎症介质

• 批准号: 7952277
• 负责人: ANDREW G GIANOUKAKIS
• 金额: $ 0.11万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7952277
• 关键词: Antibodies; Area; Autoimmune Diseases; Autoimmune Process; Blood; Blood specimen; Body part; Cell Culture Techniques; Cells; Characteristics; Clinical; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Connective Tissue; Development; Disease; Exhibits; Eye; Eye diseases; Fibroblasts; Funding; Goiter; Grant; Graves' Disease; Hashimoto Disease; Immune; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Institution; Interleukin-16; Joints; Leg; Lymphocyte; Measures; Names; Ocular orbit; Operative Surgical Procedures; Organ; Pathogenesis; Patients; Phenotype; Predisposition; Process; Reaction; Research; Research Personnel; Resources; Rheumatoid Arthritis; Severities; Skin; Source; Stream; Swelling; Symptoms; Synovial Membrane; Thyroid Gland; Tissues; United States National Institutes of Health; Upper arm; cytokine; research study; therapeutic target; wasting

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Graves' disease is a common autoimmune (inflammatory) disease. The pathogenic mechanisms underlying autoimmune disease such as Graves' disease, rheumatoid arthritis, Hashimoto's thyroiditis, etc. are largely unknown. Patients with Graves' disease are hyperthyroid (hyper) and can develop a thyroid goiter, ophthalmopathy (eye bulging) and or dermopathy (skin swelling). Our understanding of Graves' disease remains superficial and current treatment is symptom oriented. The organs and tissues named above are infiltrated by lymphocytes (immune cells). We believe that antibodies and other factors (IL-16) present in the blood stream of patients with autoimmune disease are important mediators of this inflammatory process. We are studying the factors responsible for this inflammatory response characteristic of Graves' tissues (Thyroid, Orbit, Skin), rheumatoid arthritis tissues (synovium). We will extract antibodies from the blood samples donated by the patients and use them in cell culture experiments. Primary thyrocyte and fibroblast cell cultures will be developed from thyroid or connective tissue salvaged from surgical waste. These experiments will 1) investigate the pathogenesis of Grave's inflammation and 2) identify potential therapeutic targets for interrupting the processes which leads to the development of Graves' and potentially other autoimmune diseases. Some patients with Graves' disease have elevated levels of the cytokine IL-16 in their blood. We will measure and follow (for 48 months) IL-16 levels in the blood of patients with Graves' disease and attempt to correlate these levels with the clinical severity and progression (for 48 months) of the Graves' disease. IL-16 levels will also be measured in normal control subjects. Another purpose of this study is to examine the differences between fibroblasts from the orbit (space around the eye) and fibroblasts from skin obtained from the leg, arm and other parts of the body. We have found that fibroblasts from these different body areas exhibit phenotypes that diverge. Those fibroblasts from the orbit and joint space appear particularly susceptible to inflammatory reactions. We hypothesize that it is in this susceptibility that underlies the inflammation of Graves' disease and rheumatoid arthritis, respectively.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 Graves病是一种常见的自身免疫性（炎症性）疾病。自身免疫性疾病如Graves病、类风湿性关节炎、桥本甲状腺炎等的致病机制尚不清楚。格雷夫斯病患者甲状腺功能亢进（高），并可能发展为甲状腺肿，眼病（眼睛肿胀）和/或皮肤病（皮肤肿胀）。我们对格雷夫斯病的认识仍然很肤浅，目前的治疗是以症状为导向的。上述器官和组织被淋巴细胞（免疫细胞）浸润。我们认为，自身免疫性疾病患者血流中存在的抗体和其他因子（IL-16）是这种炎症过程的重要介质。我们正在研究导致Graves'组织（甲状腺，眼眶，皮肤），类风湿性关节炎组织（滑膜）的炎症反应特征的因素。我们将从患者捐献的血液样本中提取抗体，并将其用于细胞培养实验。原代甲状腺细胞和成纤维细胞培养物将从手术废物中回收的甲状腺或结缔组织中培养。这些实验将1）研究格雷夫斯炎症的发病机制，2）确定潜在的治疗靶点，以中断导致格雷夫斯病和其他潜在自身免疫性疾病发展的过程。一些格雷夫斯病患者血液中细胞因子IL-16水平升高。我们将测量并随访（48个月）Graves病患者血液中的IL-16水平，并试图将这些水平与Graves病的临床严重程度和进展（48个月）相关联。还将在正常对照受试者中测量IL-16水平。本研究的另一个目的是检查来自眼眶（眼睛周围的空间）的成纤维细胞与来自腿部、手臂和身体其他部位的皮肤的成纤维细胞之间的差异。我们发现，这些不同身体部位的成纤维细胞表现出不同的表型。眼眶和关节间隙的成纤维细胞似乎对炎症反应特别敏感。我们推测，正是这种易感性分别构成了Graves病和类风湿性关节炎炎症的基础。