Thyrocytes Express Inflammatory Mediators

描述（由申请人提供）：对自身免疫性甲状腺疾病，桥本甲状腺炎和Graves病（GD）的认识仍然是肤浅的，目前的治疗是以症状为导向的。负责淋巴细胞浸润和自身免疫性甲状腺炎症特征的介质尚未确定。该项目的长期目标是研究甲状腺上皮细胞在炎症反应中的作用。在这里，我们提出的实验旨在：1)研究甲状腺炎症的发病机制；2)确定中断这些过程的潜在治疗靶点；3)确定自身免疫性甲状腺疾病活动的临床标志物。细胞免疫学、蛋白质化学和分子生物学技术将被用于检测免疫调节分子在体外和原位甲状腺细胞的表达。我们建议在一项对Graves病患者的48个月的前瞻性研究中测量炎症介质的血清水平，并试图将其血清水平与疾病活动联系起来。

DESCRIPTION (provided by applicant): The understanding of autoimmune thyroid diseases, Hashimoto's thyroiditis and Graves disease (GD), remains superficial and current treatment is symptom-oriented. The mediators responsible for the lymphocytic infiltration and inflammation characteristic of autoimmune thyroid glands have not been identified. The long-term objective of this project is to investigate the role of thyroid epithelial cells in the inflammatory response. Here, we propose experiments designed to 1) investigate the pathogenesis of thyroid inflammation 2) identify potential therapeutic targets for interrupting these processes and 3) identify clinical markers of autoimmune thyroid disease activity. Cellular immunology, protein chemistry and molecular biology techniques will be utilized to examine thyrocyte expression of immunomodulatory molecules in vitro and in situ. We propose to measure serum levels of inflammatory mediators and attempt to correlate their serum levels with disease activity in a 48-month prospective study of patients with Graves' disease. The candidate and mentor have worked closely for over 3 years. This relationship has led to significant production and the generation of supporting preliminary data. With the support of a research career development award, continued mentoring and the availability of a General Clinical Research Center, the candidate will be able to further investigate his findings and answer the clinically relevant questions that have arisen. During the career development period, the candidate will also complete graduate level coursework in molecular biology and translational investigation. The candidate will develop the scientific knowledge base, problem solving abilities, and technical skills which will allow him to develop into a independent physician/scientiist.