RII Track-4: Characterization of LPS-induced Hsc70 ligands as a means of defining the role of C-linked glycosylation in innate immunity.

免疫系统对感染和自身免疫性疾病的反应包括由特定化学物质控制的炎症，其中许多化学物质的产生和功能尚不清楚。该项目在格鲁吉亚大学的复合碳水化合物研究中心（CCRC）支持PI六个月。CCRC拥有无与伦比的研究专业知识和分析仪器，专注于碳水化合物分子的生化研究，包括参与炎症的分子。该奖学金允许PI访问CCRC的专业知识和先进的仪器能力，他将把这些专业知识带回马歇尔大学。在炎症背景下表征这些分子将提供关于炎症的原因和控制的重要信息，包括涉及自身免疫性疾病的炎症。技术说明该奖学金将通过支持PI努力利用CCRC的资源来评估先天免疫反应的蛋白质调节剂，从而帮助加强西弗吉尼亚州的研究能力。提供CCRC的设施和专业知识将使PI能够建立一个充满活力的研究计划，研究糖基化在西弗吉尼亚州炎症中的作用。已经表明，C-糖基化肽增强了由脂多糖（LPS）刺激的巨噬细胞样细胞分泌的促炎性细胞因子TNF#945;的产生。这表明目前未知的涉及C-连接糖基化的调节机制对于LPS/TLR 4途径的激活至关重要。作为TNF& #945;是炎症反应中产生的中心细胞因子，定义C-连接的糖基化如何调节这种细胞因子反应对于正确解决其失调至关重要。TNF的失调是炎症性疾病（如克罗恩病）所固有的。类风湿性关节炎、类风湿性关节炎和代谢综合征。

Non-technical DescriptionThe immune system's response to infection and autoimmune diseases includes inflammation that is controlled by specific chemicals, and the production and function of many of which is not clearly understood. This project supports the PI for a six-month period in the Complex Carbohydrate Research Center (CCRC) at the University of Georgia. The CCRC possesses unparalleled research expertise and analytical instrumentation focused on the biochemical study of carbohydrate molecules, including those involved in inflammation. This fellowship allows the PI access to the expertise and the advanced instrumentation capability of CCRC, and he will bring that expertise back to Marshall University. Characterization of these molecules in the context of inflammation will provide important information about the causes and control of inflammation, including inflammation involved in autoimmune disease. Technical DescriptionThis fellowship will aid in bolstering the research capacity in West Virginia by supporting the PI's efforts to use the resources at the CCRC to evaluate protein regulators of the innate immune response. Providing access to the facilities and expertise at the CCRC will enable the PI to establish a vibrant research program studying the role of glycosylation in inflammation in West Virginia. It has been shown that C-glycosylated peptides enhance the production of the proinflammatory cytokine TNFα, secreted from lipopolysaccharide (LPS)-stimulated macrophage-like cells. This indicates that a currently unknown regulatory mechanism involving C-linked glycosylation is crucial for activation of the LPS/TLR4 pathway. As TNFα is the central cytokine produced in the inflammatory response, defining how C-linked glycosylation regulates this cytokine response is critical in properly addressing its dysregulation. Dysregulation of TNFα is inherent to inflammatory diseases such as Crohn?s disease, sepsis, rheumatoid arthritis, and metabolic syndrome.