Role of Leptin in Innate Mucosal Defense from Amebiasis

瘦素在阿米巴病先天粘膜防御中的作用

基本信息

批准号：
8468611
负责人：
William A Petri
金额：
$ 40.5万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-08-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8468611
关键词：
Accounting Address Affect Affinity Amebiasis Amebic colitis Apoptosis Bangladesh Binding Birth Bone Marrow Build-it Cell Surface Receptors Cell Survival Cells Cessation of life Child Communicable Diseases Cytokine Receptors Cytoplasmic Tail Data Development Diarrhea Disease Disease susceptibility Employee Strikes Entamoeba histolytica Environment Epithelial Cells Goblet Cells Homeostasis Hormones Human Immune Immune response Immunologic Deficiency Syndromes Immunology Infection Inflammatory Intestinal Diseases Intestines Investigation JAK2 gene Knock-in Mouse Knowledge Lead Leptin Leptin deficiency Leptin receptor mutation Malnutrition Measures Mediating Mediator of activation protein Modeling Molecular Mus Mutation Natural Immunity Nutritional Nutritional status PTPN11 gene Parasites Pathogenesis Pathway interactions Physiological Population Predisposition Principal Investigator Protein-Energy Malnutrition Receptor Signaling Research Research Personnel Resistance Risk Role STAT3 gene STAT5A gene Signal Pathway Signal Transduction Site Testing Tyrosine Work Workplace cohort disease natural history extracellular genetic epidemiology human study in vivo innovation insight intestinal homeostasis leptin receptor microbiome mouse model novel nutrition prevent receptor receptor function repaired research study translational medicine

项目摘要

DESCRIPTION (provided by applicant): We will test if leptin receptor signaling in intestinal epithelial cells (IECs) protects from intestinal infection due to Entamoeba histolytica, both intrinsically within IECs by up-regulating repair pathways, and extrinsically by IEC-mediated recruitment of inflammatory cells to the intestine. Successful completion of these studies will identify the mechanism by which leptin receptor signaling acts in mucosal defense, with implications for the understanding of gut immune homeostasis. Significance: The importance of this project derives from the contribution of malnutrition to an estimated one-third of all deaths among children and 60% of deaths due to diarrhea, and to the contribution of amebiasis to severe diarrhea in children in the developing world. Innovative aspects of the proposal include that it challenges the existing paradigm that protein-energy malnutrition explains the infectious diseases susceptibility of malnourished children. In contrast this study identifies specific leptin mediated molecular pathways in intestinal epithelial cells that are altered in malnourished children and that contribute to infectious disease susceptibility The environment for the work includes active investigation of amebiasis in humans, murine models, and at the cellular level, and the Principal Investigator who has contributed to amebiasis research for over 25 years.

描述（由申请人提供）：我们将测试肠上皮细胞（IEC）中的瘦素受体信号传导是否通过上调的修复途径内在地内，可以在IEC内部固有地通过IEC诱导的炎症细胞向肠道募集到肠道上，从而在IEC内部保护肠道感染。这些研究的成功完成将确定瘦素受体信号在粘膜防御中起作用的机制，这对理解肠道免疫稳态的意义。意义：该项目的重要性来自营养不良对儿童死亡的三分之一的贡献，腹泻引起的60％的死亡以及amebiasis对发展中国家儿童严重腹泻的贡献。该提案的创新方面包括挑战蛋白质 - 能源营养不良的现有范式解释了营养不良儿童的敏感性。相反，本研究确定了特定的瘦素肠道上皮细胞中介导的分子途径在营养不良的儿童中发生了改变，并导致感染性疾病敏感性的工作包括对人类，鼠模型和细胞水平的Amebiasis的积极研究，以及在25年内为amebiasis研究贡献的主要研究者。