MicroRNA-155对牙龈卟啉单胞菌OmpH诱导巨噬细胞Pyroptosis调控机制研究

项目名称： MicroRNA-155对牙龈卟啉单胞菌OmpH诱导巨噬细胞Pyroptosis调控机制研究

项目编号： No.81470744

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 林莉

作者单位： 中国医科大学

项目金额： 67万元

中文摘要： 人牙周组织中的巨噬细胞发生Pyroptosis，一方面会降低牙周组织清除致病菌的能力，使牙周炎症不易控制，另一方面由于胞内物质流出，加重了牙周炎症反应程度，促进了牙槽骨的吸收。因此本研究拟通过构建 ompH（PG0192 和PG0193）基因敲除株和ompH回复突变菌株，用P.gingivalis W83野生株及ΔompH及回复突变菌株感染人巨噬细胞U937和人外周血巨噬细胞，同时构建 OmpH蛋白表达载体，明确P.gingivalis 外膜蛋白OmpH对巨噬细胞miR-155的表达及Pyroptosis的影响，确定miR-155对TLR4-TRIF-IFN- Caspase-11途径的调控机制，并通过动物实验验证机制的正确性。希望通过此项研究能够发现一条途径阻断P.gingivalis感染后巨噬细胞的Pyroptosis，增强牙周组织抗感染的能力，减轻牙周炎症和牙周病复发的可能性。

中文关键词： 牙龈卟啉单胞菌；OmpH蛋白；焦亡；微核糖核酸155

英文摘要： Inflammasome activation in macrophages of human periodontal tissue results in a form of cell death termed 'pyroptosis' , on the one hand it will reduce the ability to clear pathogens in periodontal tissue, so that periodontal disease is difficult to control. On the other hand , due to the consequent release of intracellular contents, the extent of periodontal inflammatory reaction is increased, and absorption of tooth-supporting alveolar bone is promoted . In this study, we will construct ompH (PG0192 and PG0193) gene knockout strains and revertant strains of P.gingivalis W83. Macrophages U937 and macrophages from human peripheral blood will be stimulated with P.gingivalis W83 ompH gene knockout strains and revertant strains.We construct OmpH protein expression vector and the macrophages are stimulated by purified proteins. We will use several methodes to evaluate the effection of OmpH protein on macrophage miR-155 expression and cell pyroptosis. Analyse the mechanisms that miR-155 regulate cell pyroptosis through TLR4-TRIF-IFN-Caspase-11 signaling pathway. Through animal experiments, we will confirm the correctness of the mechanisms about miR-155 in macrophage pyroptosis. We are going to find a way to suppress pyroptosis when macrophages are stimulated with P.gingivalis , enhance the ability of periodontal tissue resistance to infection and reduce the possibility of periodontal infection aggravation and recurrence.

英文关键词： Porphyromonas gingivals;OmpH protein;Pyroptosis;MicroRNA-155