Role of Pattern Recognition Receptors in Prostate Epithelial Inflammation

模式识别受体在前列腺上皮炎症中的作用

• 批准号: 7588277
• 负责人: PRAVEEN THUMBIKAT
• 金额: $ 10.13万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7588277
• 关键词: Advisory Committees; Affect; Bacterial Prostatitis; Behavioral; Benign Prostatic Hypertrophy; Bone Marrow Transplantation; C3H/HeJ Mouse; Classification; Clinical; Code; Collaborations; Development; Disease; Doctor of Philosophy; Environment; Epithelial; Epithelial Cells; Epithelium; Escherichia coli; Faculty; Genes; Hematopoietic; Hereditary Disease; Human; IL8 gene; Immunity; Immunohistochemistry; In Vitro; Inflammation; Inflammatory; Inflammatory Response; Intercellular adhesion molecule 1; Lead; Lipopolysaccharides; Measurement; Mediating; Medical; Mentors; Modeling; Molecular; Mus; Natural Immunity; Outcome; Pain; Pathogenesis; Pathway interactions; Patients; Pattern recognition receptor; Principal Investigator; Program Development; Prostate; Research; Research Personnel; Role; Scientist; Sensory; Signal Pathway; Signal Transduction; Site; Small Interfering RNA; Stimulus; Stromal Cells; Students; TLR4 gene; Testing; Toll-like receptors; Training; Training Programs; Transcription Factor AP-1; Universities; Up-Regulation; Urinary tract infection; Urologic Diseases; Urology; Work; career; genetic association; in vivo; inflammatory marker; member; men; new therapeutic target; novel; post-doctoral training; programs; prostatitis; public health relevance; response

DESCRIPTION (provided by applicant): This proposal describes a five-year training program for the development of an academic career in studying urologic diseases. The Principal Investigator has completed a PhD in molecular disease pathogenesis, postdoctoral training in diseases of the urinary tract and is presently in a period of transition as a junior faculty member at Northwestern University. This proposed program will lead to an understanding of the mechanisms of inflammation in the prostate gland. Dr. Anthony Schaeffer will mentor the Principal Investigator's scientific development. Dr. Schaeffer is a recognized leader in the fields of prostate inflammation and infectious diseases of the urinary tract. He is the Chair of Urology at Northwestern University and has trained numerous researchers and students. To further assist in providing guidance, an advisory committee of highly regarded medical scientists will be established to periodically review progress of the principal investigator. Research will focus on characterizing the role of toll-like receptors (TLR's) in prostate inflammatory responses and identifying the component pathways involved. Recent work by the principal investigator has shown that prostate epithelial cells express pattern recognition receptors (PRRs) like TLR4 that respond to inflammatory stimuli. The proposed studies will examine how TLR4 signaling occurs in prostate epithelial cells in response to lipopolysaccharide (LPS) from E. coli. In vitro culture models and a novel in vivo murine bacterial prostatitis model will be used. In culture, transcriptional factor activation will be studied following systematic siRNA silencing of the TLR4 signaling pathways. In vivo, chimeric mice will be used to determine the site of TLR4 functional immunity to E. coli. The Department of Urology at Northwestern University provides an ideal setting for training with close collaboration between clinical and basic scientists creating an environment conducive to the development of an academic career. PUBLIC HEALTH RELEVANCE: The proposed research will lead to a better understanding of the mechanisms of a number of urologic diseases including prostatitis and benign prostatic hyperplasia (BPH), conditions affecting millions of men.

描述(由申请人提供)： 该提案描述了一项为期五年的培训计划，旨在发展研究泌尿系统疾病的学术生涯。首席研究员已经完成了分子疾病发病机制的博士学位和泌尿系疾病的博士后培训，目前正处于西北大学初级教员的过渡期。这项拟议的计划将导致对前列腺癌炎症机制的了解。安东尼·谢弗博士将指导首席调查员的科学发展。舍弗博士是前列腺癌和尿路感染性疾病领域公认的领导者。他是西北大学泌尿系主任，培养了大量的研究人员和学生。为了进一步协助提供指导，将成立一个由备受尊敬的医学科学家组成的咨询委员会，定期审查首席调查员的进展情况。研究重点将集中在表征Toll样受体(TLR‘s)在前列腺炎性反应中的作用，并确定相关的组成部分途径。首席研究人员最近的工作表明，前列腺上皮细胞表达模式识别受体(PRRs)，如TLR4，对炎症刺激做出反应。这项拟议的研究将研究TLR4信号是如何在前列腺上皮细胞中对来自大肠杆菌的脂多糖(LPS)做出反应的。将使用体外培养模型和一种新的体内小鼠细菌性前列腺炎模型。在培养中，转录因子的激活将在系统地沉默TLR4信号通路的siRNA之后进行研究。在体内，嵌合小鼠将被用来确定TLR4对大肠杆菌的功能免疫部位。西北大学泌尿系为临床和基础科学家之间的密切合作提供了理想的培训环境，为学术事业的发展创造了有利的环境。 公共卫生相关性：拟议的研究将使人们更好地了解一些泌尿系统疾病的机制，包括前列腺炎和良性前列腺增生症(BPH)，这些疾病影响着数百万男性。