Neutrophils and Periodontitis in Diabetes

描述（由申请人提供）：糖尿病增加严重感染的风险，包括牙周炎。特定病原体的过度生长使牙周组织的稳态和组织健康的维持变得复杂。先天免疫反应防止入侵并限制感染的复杂性。当疾病作为全身性疾病的并发症发生时，如在糖尿病中，组织损伤由宿主反应（吞噬细胞介导的组织损伤）引起，这提供了有利于细菌生长和病变慢性化的微环境。炎症/免疫反应失调与糖尿病并发症，特别是牙周炎和心血管疾病的发病机制有关。暴露于外部环境和显著细菌负荷的组织，如牙周组织，风险增加。炎症组织恢复健康和稳态是由促进炎症消退的内源性激动剂介导的。牙周炎的细胞和分子机制的决议负责开始被映射。这些相同的促分解激动剂增强宿主细胞介导的抗菌活性。来自细胞（花生四烯酸）和饮食来源（ω-3脂肪酸）的前体脂肪酸底物产生脂质介质（分别为脂氧素和消退素），其反调节促炎信号。系统的牙周感染的时间研究和解决组织中的糖尿病患者是至关重要的治疗细菌引起的牙周病。这项竞争性更新R 01提案的目标是确定感染对糖尿病患者炎症消退回路的影响。我们的新假设是，通过外源性给予分解分子来恢复分解途径将解决牙周炎症并恢复稳态，从而改变微生物区系的组成。在这项提案中，我们将调查的作用机制，吞噬细胞的相互作用，在牙周组织调用先天抗菌活性和增强清除病原体在糖尿病患者。

DESCRIPTION (provided by applicant): Diabetes increases the risk of severe infections, including periodontitis. Maintenance of homeostasis and tissue health of the periodontium is complicated by overgrowth of specific pathogens. The innate immune response prevents invasion and limits the complexity of the infection. When disease occurs as a complication of systemic disease as in diabetes, tissue damage results from the host response (phagocyte mediated tissue injury), which provides a microenvironment that favors bacterial growth and the chronicity of the lesion. Dysregulated inflammatory/immune reactions have been implicated in the pathogenesis of the complications of diabetes, particularly periodontitis and cardiovascular diseases. Tissues exposed to the external environment and significant bacteria load, such as the periodontium, are at increased risk. The return of inflamed tissues to health and homeostasis is mediated by endogenous agonists that promote resolution of inflammation. The cellular and molecular mechanisms responsible for the resolution of periodontal inflammation are beginning to be mapped. These same proresolution agonists enhance host cell mediated antibacterial activity. Precursor fatty acid substrates from cells (arachidonic acid) and dietary sources (omega-3 fatty acids) yield lipid mediators (lipoxins and resolvins, respectively) that counter-regulate pro-inflammatory signals. Systematic temporal study of periodontal infection and resolution in tissues of people with diabetes is of paramount importance in the treatment of bacterially initiated periodontal disease. The goal of this competing renewal R01 proposal is to determine the impact of infection in resolution circuits of inflammation in people with diabetes. Our novel hypothesis is that restoration of resolution pathways by exogenous administration of resolving molecules will resolve periodontal inflammation and restore homeostasis modifying the composition of the microflora. In this proposal, we will investigate the mechanism of action of phagocyte interactions in the periodontium invoking innate antimicrobial activity and enhanced clearance of pathogens in people with diabetes.