Regulation of Beta-Defensin Expression in Oral Epithelia

产品说明：人β-防御素家族的抗微生物肽被认为是口腔上皮细胞和全身上皮细胞的先天免疫应答的重要组分。这些肽在口腔中可能特别重要，因为口腔中始终存在大量微生物植物群。该项目的总体工作假设是，β-防御素和其他抗菌肽以两种主要方式帮助口腔健康，第一，通过其直接的抗菌活性，第二，通过其类似尼古丁的功能刺激组织内的其他细胞对微生物挑战做出适当的反应。该项目的目标是将以前关于口腔上皮细胞中β-防御素表达和调节的工作扩展到一个更生物学的框架中。在继续体外研究的同时，两个模型系统，口腔软组织模型和牙髓模型，将用于研究β-防御素的表达，并探索其作为天然免疫中细胞相互作用的功能介质的作用，以响应暴露于口腔黏膜和病原菌。具体的假设是：1）在口腔软组织中起作用的先天性免疫机制也反映在牙髓中; 2）β-防御素在成牙本质细胞中表达，成牙本质细胞是充当牙髓内屏障的上皮样细胞; 3）β-防御素介导上皮细胞之间的通讯（或成牙本质细胞）和树突状细胞（连接先天免疫和适应性免疫的主要细胞）;（4）β-在口腔上皮和牙髓中表达的防御素是不同的，反映了上皮细胞之间功能和相互作用的区域差异（或成牙本质细胞）和它们各自的树突细胞群体。这些研究将导致对先天免疫作用的新见解和口腔感染治疗药物开发的新潜在靶点。

DESCRIPTION: Antimicrobial peptides of the human beta-defensin family are recognized as important components of the innate immune responses of oral epithelia and epithelia throughout the body. These peptides may be particularly important in the oral cavity where microbial flora is present in high numbers at all times. The overall working hypothesis for this project is that beta-defensins, and other antimicrobial peptides, aid oral health in two main ways, first, by their direct antimicrobial activity, and second, by their cytokine-like functions to stimulate other cells within the tissue to respond appropriately to the microbial challenge. The goal of this project is to expand previous work on beta-defensin expression and regulation in oral epithelial cells into a more biological framework. While continuing in vitro studies, two model systems, an oral soft tissue model and a tooth pulp model, will be used to investigate the expression of beta-defensins and to explore their role as functional mediators of cell interactions in innate immunity in response to exposure to oral commensal and pathogenic bacteria. The specific hypotheses are 1) that innate immune mechanisms that function within the oral soft tissue are also reflected in the tooth pulp; 2) that beta-defensins are expressed in odontoblasts, the epithelial-like cells that serve as the barrier within pulp, 3) that beta-defensins mediate communication between epithelial cells (or odontoblasts) and dendritic cells, the primary cells that bridge innate and adaptive immunity; and 4) that beta-defensins expressed in oral epithelium vs. tooth pulp are different and reflect regional differences in function and interaction between epithelial cells (or odontoblasts) and their respective populations of dendritic cells. These studies will lead to new insights on the role of innate immunity and new potential targets for therapeutic drug development for oral infections.