Balancing expression of PRRs in epithelial innate immune responses to bacteria

平衡上皮对细菌先天免疫反应中 PRR 的表达

• 批准号: 8270367
• 负责人: Whasun Oh Chung
• 金额: $ 34.4万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8270367
• 关键词: Address; Bacteria; CCL20 gene; CXCL5 gene; Cell surface; Characteristics; Communication; Data; Environment; Enzymes; Epithelial; Epithelial Cells; Epithelial Receptor Cell; Equilibrium; Exposure to; Goals; Homeostasis; Immune response; Individual; Inflammatory Response; Investigation; Lead; Ligands; MAP Kinase Gene; MAPK Signaling Pathway Pathway; Mediator of activation protein; Molecular; Mouth Diseases; Natural Immunity; Oral cavity; Pathogenicity; Pattern; Pattern recognition receptor; Periodontal Diseases; RNA Interference; Regulation; Signal Pathway; Signal Transduction; Small Interfering RNA; Sum; Testing; Tissues; Work; abstracting; cytokine; mRNA Expression; microbial; new therapeutic target; novel; oral bacteria; oral cavity epithelium; pathogenic bacteria; prevent; protein expression; receptor; response

Abstract Epithelial tissues function as the first line of defense between the host and the outside environment, which includes pathogenic and non-pathogenic bacteria. In the oral cavity, epithelial tissues are constantly exposed to a variety of bacteria, but most individuals maintain a healthy homeostasis. However, little is known about how this homeostatic relationship is orchestrated. Preliminary data utilizing RNA interference via siRNA suggest that compensatory mechanisms exist among Pattern Recognition Receptors (PRRs). Additionally, when a PRR is activated, the expression of other PRRs increases. These data strongly suggest that epithelial cells have novel mechanisms to balance expression of PRRs in response to bacteria. The hypothesis to be tested in this proposal is that PRRs balance their responses in epithelial innate immunity upon exposure to oral bacteria depending on the characteristics and pathogenicity of the bacteria. The goal of this work is to understand cross- communication between epithelial receptors as well as the specific signaling pathways that are involved in the PRR cross-communication in epithelial innate immunity. This proposal will investigate how various epithelial cell receptors compensate for the activation or absence of one another in inducing appropriate epithelial innate immune responses. In addition, this proposal will examine if activation of PRRs differentially regulate the NF¿B and MAPK signaling pathways, thus tailoring epithelial innate immune responses to individual bacterium. Since bacteria have multiple Microbial-Associated Molecular Patterns and epithelial cells express multiple PRRs, it is reasonable to expect that there is cross-communication and balancing between these PRRs in epithelial responses to various bacteria in order to induce appropriate innate immune responses. The proposed studies will lead to a better understanding of the way oral epithelia produce appropriate innate immune responses to pathogenic and non-pathogenic bacteria, guiding a way to new therapeutic targets to prevent and treat oral diseases, such as periodontal disease.

摘要 上皮组织作为宿主与外界环境之间的第一道防线， 其包括致病性和非致病性细菌。在口腔中，上皮组织是 他们经常暴露在各种细菌中，但大多数人保持健康的体内平衡。 然而，很少有人知道这种自我平衡的关系是如何协调的。初步数据 通过siRNA利用RNA干扰表明，模式之间存在代偿机制， 识别受体（PRRs）。此外，当PRR被激活时，其他PRR的表达也会被抑制。 增大这些数据有力地表明，上皮细胞有新的机制来平衡 PRRs的表达对细菌的应答。本提案中要检验的假设是， 在暴露于口腔细菌后平衡其上皮先天免疫反应， 细菌的特性和致病性。这项工作的目的是了解跨- 上皮受体之间的通讯以及参与的特定信号通路 在上皮先天免疫的PRR交叉通讯中。该提案将调查各种 上皮细胞受体补偿彼此的激活或缺失， 上皮先天免疫反应。此外，本提案将审查是否启动PRR， 差异调节NF B和MAPK信号通路，从而定制上皮先天免疫 对单个细菌的反应。由于细菌具有多种微生物相关的分子模式， 并且上皮细胞表达多种PRR，因此可以合理地预期存在交叉交流 以及在上皮对各种细菌的反应中这些PRR之间的平衡， 适当的先天免疫反应。拟议的研究将有助于更好地了解 口腔上皮细胞对致病性和非致病性的天然免疫反应的方式 细菌，指导一种新的治疗目标，以预防和治疗口腔疾病，如牙周病， 疾病