IL-1R1 promoter complex in the neuroendocrine, nervous, and immune systems

神经内分泌、神经和免疫系统中的 IL-1R1 启动子复合物

• 批准号: 8079335
• 负责人: Ning Quan
• 金额: $ 8.4万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-06 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8079335
• 关键词: Alzheimer' s Disease; Amino Acid Sequence; Anti-Inflammatory Agents; Anti-inflammatory; Antigen Presentation; Arthritis; Attenuated; Autoimmune Diseases; Behavior; Binding Sites; Biological; Biological Assay; Biology; Brain Ischemia; CREB1 gene; Cell Line; Cells; Cellular Immunity; Characteristics; Complex; Databases; Development; Disease; Exons; Fever; Foundations; Genbank; Genes; Genetic; Genetic Transcription; Glucocorticoid Receptor; Glucocorticoids; Hand; Hormones; Host Defense; Human; Hypothalamic structure; Immune response; Immune system; In Situ Hybridization; Infectious Agent; Inflammation; Inflammatory; Interleukin-1; Interleukin-1 Receptors; Knowledge; Laboratories; Lead; Learning; Location; Lymphocyte Activation; Maps; Mediating; Memory; Messenger RNA; Mus; Neurons; Neurosecretory Systems; Neurotransmitters; Nucleic Acid Regulatory Sequences; Pathogenesis; Pattern; Peptides; Phase; Phenotype; Physiological; Play; Process; Promoter Regions; RNA Splicing; Regulation; Regulatory Element; Research; Role; Screening procedure; Signaling Molecule; Staging; Stress; Structure; Sympathetic Nervous System; System; Tissues; Transcription Initiation Site; Transcriptional Regulation; Work; base; cell type; conditioned fear; deletion analysis; genetic element; in vivo; interleukin-1 receptor type I; interleukin-1 receptor type II; nerve injury; promoter; receptor; response; transcription factor

DESCRIPTION (provided by applicant): Type I interleukin-1 receptor (IL-1R1) is the functional receptor for IL-1. IL-1 mediates numerous activities in the neuroendocrine, nervous, and immune systems. The transcriptional regulation of IL-1R1 is poorly understood. Current work in our lab has identified three promoters that control the transcription of IL-1R1 in mouse. The activities of these IL-1R1 promoters are tissue-specific, cell type-specific and dependent on developmental stages. In addition, these promoters are found to be regulated by exogenous as well as endogenous genetic regulatory elements. In vivo, the activities of the three murine IL-1R1 promoters showed distinct distribution patterns. Further, these IL-1R1 promoters are differentially regulated by signaling molecules, such as glucocorticoids. A species comparison study between murine and human IL-1R1 structures has been conducted. Aligning the resulting human and murine IL-1R1 promoter regions revealed a conserved framework by which IL-1R1 gene in both species are likely to be regulated by conserved regulatory sequences. These preliminary discoveries lead us to define a genetic region termed IL-1R1 promoter complex. The central hypotheses of this application are: 1) the level and type of IL-1R1 mRNAs expressed in a given cell are regulated by the IL-1R1 promoter complex; 2) the transcriptional control mechanisms in the IL-1R1 promoter complex determine the tissue- and cell type-specific expression of IL-1R1; and 3) IL-1R1 promoter complex contributes to the precise response characteristics of IL-1R1-bearing cells when they are stimulated by signaling molecules. We will pursue the following specific aims: 1) Determine the pattern of distribution of the promoter-specific IL-1R1 expression; 2) Elucidate transcriptional control mechanisms of the IL-1R1 promoter complex; and 3) Investigate promoter activity of IL-1R1 gene in selected cell types after the cells are stimulated by different signaling molecules. The results will reveal the transcriptional mechanisms that allow tissue-specific and cell type-specific expression and regulation of IL-1R1 that may be critical for the vast diversity of IL-1R1 function in multiple systems. This study will contribute significantly to IL-1R1 biology and provide a new foundation for our understanding of how IL-1R1 transcription might be involved in pathogenesis. for "IL-1R1 promoter complex in the neuroendocrine, nervous, and immune system" This study investigates the transcriptional mechanisms that control the expression of the type 1 interleukin-1 receptor. This receptor is important for many functions in the nervous, neuroendocrine, and immune systems. The results will provide a foundation for the understanding of how dysregulation of the expression of type 1 interleukin-1 receptor may be involved in the pathogenesis of diseases in multiple systems.

描述（由申请人提供）：I型白介素-1受体（IL-1R1）是IL-1的功能受体。 IL-1介导了神经内分泌，神经和免疫系统中的许多活动。 IL-1R1的转录调控知之甚少。我们实验室中的当前工作确定了控制小鼠中IL-1R1转录的三个启动子。这些IL-1R1启动子的活性是组织特异性，细胞类型特异性的，并且取决于发育阶段。此外，发现这些启动子受外源和内源性遗传调节元件的调节。在体内，三个鼠IL-1R1启动子的活性显示出不同的分布模式。此外，这些IL-1R1启动子通过信号分子（例如糖皮质激素）差异调节。已经进行了鼠与人IL-1R1结构之间的物种比较研究。对齐所得的人和鼠IL-1R1启动子区域的对齐揭示了一个保守的框架，通过该框架，这两种物种中的IL-1R1基因可能受保守的调节序列调节。这些初步发现使我们定义了称为IL-1R1启动子复合物的遗传区域。该应用的中心假设是：1）在给定细胞中表达的IL-1R1 mRNA的水平和类型由IL-1R1启动子复合物调节； 2）IL-1R1启动子复合物中的转录控制机制决定了IL-1R1的组织和细胞类型特异性表达； 3）IL-1R1启动子复合物在通过信号分子刺激IL-1R1细胞的精确响应特征。我们将追求以下特定目的：1）确定启动子特异性IL-1R1表达的分布模式； 2）阐明IL-1R1启动子复合物的转录控制机制； 3）研究细胞通过不同的信号分子刺激细胞类型中IL-1R1基因的启动子活性。结果将揭示转录机制，这些机制允许组织特异性和细胞类型特异性表达和IL-1R1调节，这对于多个系统中IL-1R1的巨大多样性可能至关重要。这项研究将对IL-1R1生物学产生重大贡献，并为我们理解IL-1R1转录如何参与发病机理提供了新的基础。对于“神经内分泌，神经和免疫系统中的IL-1R1启动子复合物”，本研究研究了控制1型白介素-1受体表达的转录机制。该受体对于神经，神经内分泌和免疫系统的许多功能很重要。结果将为理解1型白介素-1受体表达的失调如何参与多个系统中疾病的发病机理。