Interaction of Retinoid X Receptors and NOD-Like Receptors in Colon Inflammation

类维生素A X 受体和NOD 样受体在结肠炎症中的相互作用

• 批准号: 8596049
• 负责人: Agnieszka Dorota Truax
• 金额: $ 5.22万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8596049
• 关键词: Acetyltransferase; Affect; Agreement; Apoptosis; Attention; Attenuated; Binding; Binding Sites; Cell Line; Cells; Chromatin; Chronic; Chronic Disease; Co-Immunoprecipitations; Colitis; Colon; Colon Carcinoma; Computer Simulation; Containment; Crohn' s disease; DNA; Data; Diet; Disease; Electrophoretic Mobility Shift Assay; Environment; Enzymes; Equilibrium; Excision; Family; Family member; Gene Expression; Genes; Genetic Polymorphism; Genetic Transcription; Goals; Histones; Homeostasis; Hormones; Immune; Immune response; Immunosuppressive Agents; Indium; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory Response; Leucine-Rich Repeat; Maintenance; Malignant Neoplasms; Mediating; Metabolic; Methyltransferase; Modeling; Modification; Molecular; Mus; Mutate; NF-kappa B; Natural Immunity; Nuclear; Nuclear Receptors; Nucleotides; Pathway interactions; Pattern; Phosphorylation; Phosphotransferases; Play; Prevention; Process; Production; Promoter Regions; Protein Family; Proteins; RXR; Recruitment Activity; Regulation; Regulatory Element; Reporting; Research; Retinoic Acid Receptor; Role; Serine; Signal Pathway; Signal Transduction; Sulfonic Acids; Syndrome; Testing; Toll-like receptors; Transcriptional Regulation; Tretinoin; Trinitrobenzenes; Ulcer; Up-Regulation; Vitamin A; Vitamin A Deficiency; Vitamins; chromatin immunoprecipitation; cytokine; genetic association; in vivo; insight; macrophage; microbial; monocyte; multicatalytic endopeptidase complex; novel; p65; pathogen; promoter; public health relevance; receptor; receptor binding; receptor function; research study; response; sensor; transcription factor; tumor

DESCRIPTION (provided by applicant): Chronic inflammatory syndromes arise as a consequence of genetic polymorphism in combination with environment, pathogens and diet. Colitis is a form of inflammatory bowel diseases (IBD) that is characterized by ulcers in the colon. IBD are commonly associated with the exaggerated production of inflammatory cytokines, which are regulated by the activation of various cell signaling pathways and the NF-kB family of transcription factors. The NLR (nucleotide binding domain and leucine-rich-repeat-containing or NOD-like receptor) family of proteins has received much attention in IBD research due to the genetic association of NOD2 with Crohns' disease. We found that NLRP12, a new NLR family member acts as a negative regulator of inflammation by suppressing NF-kB activation via multiple mechanisms, including the induction of proteasome mediated degradation of NIK (NF-kB inducing kinase). In addition to negative regulators of innate immunity, studies have shown that nuclear receptors (NRs) can suppress inflammation, tumor formation, and induce cell apoptosis. A greater understanding of how NLRP12 can interact with NRs is important in understanding the processes that are crucial in the maintenance of homeostasis and the reduction of inflammation in a healthy gut. We employed an in silico protein interactome analysis and found that NLRP12 can interact with NRs. In addition, we localized several potential NR regulatory elements in the promoter of NLRP12. The goal of this proposal is to determine the intersection of NRs with NLRP12 in regulating NF-kB activation in colon.

描述（由申请人提供）：慢性炎症综合征是遗传多态性与环境、病原体和饮食相结合的结果。结肠炎是一种炎症性肠病（IBD），其特征在于结肠溃疡。IBD通常与炎性细胞因子的过度产生相关，其通过各种细胞信号传导途径和转录因子的NF-kB家族的激活来调节。NLR（nucleotide binding domain and leucine-rich-repeat-containing or NOD-like receptor）蛋白家族由于NOD2与克罗恩病的遗传关联而在IBD研究中受到了广泛关注。我们发现，NLRP 12，一个新的NLR家族成员，通过多种机制抑制NF-κ B活化，包括诱导蛋白酶体介导的NIK（NF-κ B诱导激酶）降解，作为炎症的负调节因子。除了先天免疫的负调节因子外，研究表明核受体（NRs）可以抑制炎症、肿瘤形成并诱导细胞凋亡。更好地了解NLRP 12如何与NR相互作用，对于理解在健康肠道中维持稳态和减少炎症至关重要的过程非常重要。我们采用计算机蛋白质相互作用组分析，发现NLRP 12可以与NR相互作用。此外，我们在NLRP 12的启动子中定位了几个潜在的NR调控元件。该提案的目标是确定NRs与NLRP 12在调节结肠中NF-κ B活化中的交叉点。