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。维持体内平衡和牙周组织健康是复杂的特定病原体的过度生长。先天免疫反应阻止了入侵，限制了感染的复杂性。当疾病作为全身性疾病（如糖尿病）的并发症发生时，宿主反应（吞噬细胞介导的组织损伤）导致组织损伤，这提供了一个有利于细菌生长和病变慢性的微环境。失调的炎症/免疫反应与糖尿病并发症的发病机制有关，特别是牙周炎和心血管疾病。暴露于外部环境和大量细菌负荷的组织，如牙周组织，风险增加。炎症组织恢复健康和体内平衡是由内源性激动剂介导的，可以促进炎症的消退。牙周炎症解决的细胞和分子机制开始被绘制出来。这些相同的溶解激动剂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（欧米伽-3脂肪酸）产生脂质介质（分别是脂质毒素和溶解蛋白），它们可以反调节促炎信号。系统地研究牙周感染和糖尿病患者组织的消退在治疗细菌性牙周病中是至关重要的。这一竞争性更新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，通过外源性给予溶解分子来恢复溶解途径将解决牙周炎症，并通过改变微生物群的组成来恢复体内平衡。在本研究中，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，以激活先天抗菌活性并增强病原体的清除。

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.