Neutrophils and Periodontitis in Diabetes

描述(申请人提供)：糖尿病会增加严重感染的风险，包括牙周炎。牙周组织的动态平衡和组织健康的维持因特定病原体的过度生长而变得复杂。先天免疫反应可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，如糖尿病，组织损伤是由宿主反应(吞噬细胞介导的组织损伤)引起的，宿主反应提供了有利于细菌生长和病变慢性化的微环境。炎症/免疫反应失调参与了糖尿病并发症的发病机制，尤其是牙周炎和心血管疾病。暴露在外部环境和大量细菌负载下的组织，如牙周组织，风险更高。炎症组织的恢复健康和动态平衡是由促进炎症消退的内源性激动剂介导的。负责解决牙周炎的细胞和分子机制正开始被绘制出来。这些促分解激动剂可增强宿主细胞介导的抗菌活性。来自细胞的前体脂肪酸底物(花生四烯酸)和饮食来源的(omega-3脂肪酸)产生的脂类介体(分别是脂素和分解素)可以反调节促炎信号。对糖尿病患者牙周组织中牙周感染和消退的系统时间研究对于细菌性牙周病的治疗是至关重要的。这项相互竞争的更新R01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，可以缓解牙周炎症，恢复动态平衡，改变微生物区系的组成。在这项提案中，我们将研究糖尿病患者牙周组织中吞噬细胞相互作用的作用机制，这些作用激活了天然的抗微生物活性和增强了病原体的清除。

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.