Regulation of Beta-Defensin Expression in Oral Epithelia

描述：人类β-防御素家族的抗菌肽被认为是口腔上皮细胞和全身口腔上皮细胞天然免疫反应的重要组成部分。这些多肽在口腔中可能特别重要，因为口腔中微生物的数量一直很多。该项目的总体工作假设是，β-防御素和其他抗菌肽主要通过两种方式帮助口腔健康，一是通过它们的直接抗菌活性，二是通过它们的细胞因子样功能来刺激组织内的其他细胞对微生物的挑战做出适当的反应。该项目的目标是将先前关于口腔上皮细胞中β-防御素表达和调控的工作扩展到更具生物学意义的框架中。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，将被用来研究β-防御素的表达，并探讨它们作为细胞相互作用的功能性介质在口腔共生和致病菌暴露中的作用。具体的假设是1)在口腔软组织内发挥作用的先天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，上皮样细胞在牙髓中起屏障作用；3)β-防御素介导上皮细胞(或成牙本质细胞)和树突状细胞之间的通讯，树突状细胞是连接固有免疫和获得性免疫的初级细胞；以及4)β-防御素在口腔上皮细胞和牙髓中表达的不同，反映了上皮细胞(或成牙本质细胞)和它们各自的树突状细胞之间的功能和相互作用的地区差异。这些研究将为先天免疫的作用带来新的见解，并为口腔感染的治疗药物开发新的潜在靶点。

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.