Peripheral and Central Inflammatory Signals in the Sickness Response

疾病反应中的外周和中枢炎症信号

基本信息

批准号：
7998399
负责人：
BRENT E WISSE
金额：
$ 8.5万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-03-01 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7998399
关键词：
Affect Animals Anorexia Behavior Biological Response Modifiers Body Weight Body Weight decreased Bone Marrow Bone Marrow Stem Cell Bone Marrow Transplantation Cells Characteristics Chronic Competence Cytokine Signaling Data Disease Eating Endothelial Cells Energy Intake Expenditure Experimental Models Genetic Genotype Goals Hypothalamic structure Immune Immune response Impairment Inflammation Inflammation Mediators Inflammatory Inflammatory Response Laboratories Mediating Mediator of activation protein Melanocortin 4 Receptor Methods Molecular Mus Neurons Obesity Outcome Measure Pathway interactions Peripheral Role Signal Pathway Signal Transduction Stimulus Structure of nucleus infundibularis hypothalami TLR4 gene Techniques Tissues Transplantation Wild Type Mouse brain tissue cadherin 5 cell type cytokine energy balance irradiation laser capture microdissection mRNA Expression mouse model mutant mouse model nestin protein response wasting

项目摘要

DESCRIPTION (provided by applicant): Peripheral and Central Inflammatory Signals in the sickness Response This application investigates the hypothesis that inflammation-induced negative energy balance is mediated by mechanisms dependent on cytokine signaling pathways within brain tissue. Systemic inflammatory conditions cause marked weight loss yet the necessity of cytokines in 'sickness' remains unclear and the interaction between inflammation and neuronal regulators of energy balance remains unknown. The Specific Aims seek to determine the role of key inflammatory pathways in mediating the 'sickness response' by determining 1) whether inflammatory signals in brain tissue are necessary and sufficient to mediate the sickness response', and whether inflammatory signaling in neurons and endothelial cells is necessary to cause 'sickness', and 2) whether hypothalamic melanocortin signaling is necessary for 'sickness' to occur. To accomplish these objectives, studies are proposed using a variety of mutant mouse models to evaluate 'sickness' using methods established in the laboratories of the applicant and the Consultants participating in this proposal, including determining energy intake and expenditure, quantifying hypothalamic and circulating cytokines and bone marrow transplantation to alter the genotype of circulating immune cells. These aims make an important contribution to understanding the mechanism whereby inflammation affects energy balance and may identify potential therapies for disorders ranging from obesity to chronic wasting illnesses.

描述（由申请人提供）：疾病反应中的周围和中枢炎症信号本申请研究了以下假设：炎症诱导的负能量平衡是由依赖脑组织内细胞因子信号通路的机制介导的。全身性炎症状况会导致体重减轻，但“疾病”中细胞因子的必要性尚不清楚，炎症与能量平衡的神经元调节剂之间的相互作用仍然未知。具体目的旨在确定关键炎症途径在介导“疾病反应”中的作用1）确定脑组织中的炎症信号是否必要且足以介导疾病的反应”，以及神经元和内皮细胞中的炎症信号是否需要引起“疾病”，以及是否需要发生假设糖浆毒素'''''''''为了实现这些目标，使用各种突变小鼠模型提出了研究，以使用申请人实验室和参与该提案的顾问中建立的方法来评估“疾病”，包括确定能量摄入和支出，量化下丘脑和循环的细胞因子和循环的细胞因子和骨髓骨髓移植，以改变循环中的循环型循环型。这些目标为理解炎症影响能量平衡的机制做出了重要贡献，并可能确定从肥胖到慢性浪费疾病等疾病的潜在疗法。