REGULATION OF RETROOCULAR CONNECTIVE TISSUE: INTERLEUKIN IL-16 LEVELS IN PATI

眼后结缔组织的调节：PATI 中白细胞介素 IL-16 水平

• 批准号: 8174470
• 负责人: TERRY J SMITH
• 金额: $ 4.42万
• 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: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8174470
• 关键词: Autoimmune Process; Characteristics; Computer Retrieval of Information on Scientific Projects Database; Connective Tissue; Data; Deposition; Exhibits; Fibroblasts; Funding; Grant; Heterogeneity; Hyaluronan; IL8 gene; Inflammation; Inflammatory; Institution; Interleukin-16; Interleukin-6; Interleukins; Laboratories; Ligands; Lymphocyte; Metabolic; Molecular; Ocular orbit; Pathogenesis; Population; Regulation; Research; Research Personnel; Resources; Role; Signal Transduction; Source; T-Lymphocyte; TNFRSF5 gene; Testing; United States National Institutes of Health; base; cytokine; mast cell; response; retroocular; thyroid associated ophthalmopathies

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. To determine the role of fibroblasts heterogeneity in the pathogenesis of Graves' ophthalmopathy (GO). GO is an autoimmune process associated with lymphocyte and mast cell recruitment resulting in hyaluronan deposition and inflammation of the orbit. This laboratory has demonstrated that orbital fibroblasts exhibit phenotypic attributes that distinguish them from other fibroblasts. The hypothesis to be tested in this proposal is that exaggerated responses of the orbital fibroblasts to pro-inflammatory cytokines and CD40 activation by its ligand (CD40L) in fibroblasts subsets represent the molecular basis of GO. Populations of orbital fibroblasts subsetted according to Thy-1 expression or its absence both display surfact CD40 but exhibit distinct metabolic characteristics. Moreover, CD40 activation by CD40L enhances IL-6 and IL-8 expression. Data presented in this application support the concept that CD40 expression represents a major signal conduit for orbital fibroblasts activation by T lymphocytes and mast cells.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 确定成纤维细胞异质性在格雷夫斯眼病（GO）发病机制中的作用。 GO 是一种与淋巴细胞和肥大细胞募集相关的自身免疫过程，导致透明质酸沉积和眼眶炎症。该实验室已证明眼眶成纤维细胞表现出与其他成纤维细胞不同的表型属性。本提案要测试的假设是，成纤维细胞亚群中眼眶成纤维细胞对促炎细胞因子及其配体 (CD40L) 激活 CD40 的过度反应代表了 GO 的分子基础。根据 Thy-1 表达或缺失进行分组的眼眶成纤维细胞群均显示表面 CD40，但表现出不同的代谢特征。此外，CD40L 激活 CD40 可增强 IL-6 和 IL-8 的表达。本申请中提供的数据支持这样的概念：CD40表达代表T淋巴细胞和肥大细胞激活眼眶成纤维细胞的主要信号管道。