INFLAMMATION AND SYNOVIAL CELL PROLIFERATION IN RHEUMATOID ARTHRITIS

类风湿关节炎中的炎症和滑膜细胞增殖

• 批准号: 3804435
• 负责人: S SPENCE MCCACHREN
• 金额: --
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3804435
• 关键词: DNA; antiarthritic agent; antiinflammatory agents; binding proteins; biological signal transduction; biopsy; cellular pathology; collagenase; colony stimulating factor; diacylglycerols; genetic regulation; genetic transcription; high performance liquid chromatography; histochemistry /cytochemistry; human tissue; immunopathology; inflammation; interferons; interleukin 1; messenger RNA; neoplastic cell culture for noncancer research; nucleic acid hybridization; nucleic acid probes; oligonucleotides; oncogenes; oncoproteins; osteoarthritis; phagocytes; plasminogen activator; platelet derived growth factor; protein kinase C; rheumatoid arthritis; skeletal pharmacology; synovial membrane; synovitis; thin layer chromatography; tissue /cell culture; transforming growth factors; tumor necrosis factor alpha; tumor necrosis factor beta

The long range goal of this proposal is to begin to understand the regulation of synovial cell proliferation and functional in rheumatoid arthritis. Factors produced in the complex cellular microenvironment of the rheumatoid joint play a central role in the control of cellular proliferation and in the synthesis and release of inflammatory mediators. We propose to study these processes in situ using hybridization histochemistry and in vitro focusing on signal transduction and gene regulation. Synthetic oligonucleotide probes for growth factors (IL-1, TNF, CSFs, PDGF, TGF, IFN), genes associated with proliferation (myc, fos, ODC) and inflammatory mediators (plasminogen activator, collagenase) will be used to identify sites of cellular synthesis in sections of synovial biopsies. The role of the diacy1g1ycerol- protein kinase C pathway in synovial cell responses to specific factors will be determined by direct measurement of diacy1g1ycerol and assessment of phosphoprotein changes in the cells. The expression and mechanism of regulation of the genes encoding c-myc, c-fos, ODC, plasminogen activator and collagenase will be determined in isolated synovial lining cells in response to specific factors. This group of studies may identify novel targets for therapeutic intervention in rheumatoid arthritis.

这项建议的长期目标是开始理解 滑膜细胞增殖和功能的调节 类风湿关节炎。在复杂的细胞中产生的因子 类风湿关节微环境在类风湿关节炎发病中的核心作用 细胞增殖的控制以及在合成和 释放炎症介质。我们建议对这些问题进行研究 原位杂交组织化学和体外过程 专注于信号转导和基因调控。合成的 生长因子(IL-1、肿瘤坏死因子、CSF、 PDGF、转化生长因子、干扰素)、与增殖相关的基因(myc、fos、 和炎症介质(纤溶酶原激活剂、 胶原酶)将被用来确定细胞合成的位置 滑膜活检的切片。双甘油的作用- 滑膜细胞特异性反应中的蛋白激酶C途径 系数将通过直接测量以下各项确定 甘油三酯与高血压病患者磷蛋白变化的研究 细胞。基因的表达及其调控机制 编码c-myc、c-fos、ODC、纤溶酶原激活物和 将在分离的滑膜衬里细胞中测定胶原酶 对特定因素的反应。这组研究可能会发现 类风湿性关节炎治疗干预的新靶点。