Inflammatory responses of vascular cells

血管细胞的炎症反应

• 批准号: 8242739
• 负责人: PAUL E DICORLETO
• 金额: $ 182.78万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8242739
• 关键词: Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Area; Atherosclerosis; Binding; Biochemistry; Blood Vessels; Cardiovascular Pathology; Cell Culture Techniques; Cell Line; Cell physiology; Cells; Cellular biology; Chairperson; Chronic; Clinic; Complex; Cytokine Receptors; Development; Discipline; Endothelial Cells; Event; Foxes; Gene Expression; Genes; Goals; HOXA9 gene; Immunology; Infection; Inflammation; Inflammatory; Inflammatory Response; Injury; Interferons; Interleukin-1; Interleukins; International; Invaded; Knowledge; Lead; Leadership; Leukocytes; Lipoproteins; Lymphocyte; Molecular; Organism; Pathology; Pathway interactions; Phosphorylation; Play; Post-Transcriptional Regulation; Process; Production; Proteins; Receptor Signaling; Regulation; Research; Research Institute; Research Personnel; Resolution; Review Committee; Role; Services; Signal Pathway; Signal Transduction; Site; Surface; Systems Biology; Talents; Time; Tissues; Toll-like receptors; Transcript; Transcriptional Regulation; Translations; Trauma; Tumor Necrosis Factor Receptor; Vascular Diseases; atherogenesis; base; cost effective; cytokine; experience; interest; macrophage; meetings; microbial; monocyte; novel; programs; receptor; response; trafficking; transcriptional coactivator p75; vascular inflammation

Chronic inflammation is a principal cause of atherosclerosis and other vascular diseases. Inflammation is an orchestrated response to trauma incited by tissue injury or microbial invasion of the host. The inflammatory response is initiated by cytokines that induce cascades of signaling events culminating in the expression of new gene products, some of them toxic to invading organisms. Uncontrolled production or accumulation of inflammatory products can be injurious to the host organism. Mechanisms have evolved that limit the production of these products and permit resolution of the inflammatory response. The central hypothesis of this continuing Program Project is that pro- and anti-inflammatory processes in vascular cells are tightly regulated by endogenous signaling pathways, and their dysregulation contributes to vascular diseases such as atherosclerosis. We will investigate this hypothesis through three highly focused, but well-integrated projects led by a team of accomplished experts in diverse areas of vascular inflammation. In Project 1, Dr. Xiaoxia Li investigates the macrophage signaling pathways initiated by the interleukin-1R (IL-1 receptor)/TLR (Toll-like receptor) superfamily which can lead to either a pro-inflammatory, transcriptional program of gene expression, or an anti-inflammatory, post-transcriptional program. The theme of pro- and anti-inflammation, and also post-transcriptional regulation, continues in Project 2, led by Dr. Paul Fox, which focuses on a distinct post-transcriptional mechanism in monocyte/macrophages in which interferon-??induces phosphorylation- dependent formation of a complex that binds select inflammatory transcripts and inhibits their translation. The goal of Project 3, led by Dr. Paul DiCorleto, is to understand the role of the tumor necrosis factor receptor p75 and the transcription factor HOXA9 in the transcriptional regulation of pro-inflammatory genes in endothelial cells. Three scientific cores (Cell Culture, Atherosclerosis and Lipoprotein Analysis, and Macromolecular Interaction) and an Administration Core will provide multi-project support, expertise, and service in a cost-effective manner, which will significantly strengthen each investigator's research effort.

慢性炎症是动脉粥样硬化和其他血管疾病的主要原因。炎症是对组织损伤或宿主微生物侵袭引起的对创伤的策划反应。炎症反应是由细胞因子引发的，该细胞因子诱导一系列信号事件，最终导致新基因产物的表达，其中一些对入侵生物有毒。炎症产品的不受控制的产生或积累可能对宿主生物有害。机制已经进化出来，限制了这些产品的产生，并允许解决炎症反应。这个持续计划项目的中心假设是，血管细胞中的促和抗炎过程受内源性信号通路严格调节，它们的失调有助于血管性疾病，例如动脉粥样硬化。我们将通过三个高度重点但良好的项目来调查这一假设，该项目由一支在血管炎症的各个领域成熟的专家团队领导。在项目1中，小氧化博士研究了由白介素1R（IL-1受体）/TLR（Tollike受体）超家族启动的巨噬细胞信号通路，该途径可以导致促炎的基因表达的转录，或抗炎后，抗炎后，分别记录后，分别记录。保罗·福克斯（Paul Fox）的领导下，在项目2中持续了亲和抗炎的主题，以及转录后调节的主题，该项目的重点是单核细胞/巨噬细胞中独特的转录后机制，其中干扰素 - 诱导磷酸化依赖性形成的复合物，可融合炎症性转录的复合物的依赖性形成，并构成其易药性转录和构成的翻译。 Paul Dicorleto博士领导的项目3的目标是了解肿瘤坏死因子受体p75的作用和转录因子HOXA9在内皮细胞中促炎基因的转录调控中的转录因子HOXA9。三个科学核心（细胞培养，动脉粥样硬化和脂蛋白分析以及大分子相互作用）和给药核心将以具有成本效益的方式提供多项目的支持，专业知识和服务，这将显着增强每个研究者的研究工作。