MAPKs信号通路在布鲁氏菌致炎过程中的分子机制研究

Mitogen-activated protein kinase (MAPK) is the most important intracellular signal pathways that can be activated by varieties of inflammatory cytokines and plays an important role in regulate inflammation.Brucella outer membrane protein OMP25 is related to inflammation cytokine,Funded by the National Natural Science Foundation. protein of OMP25 has cytotoxicity and can lead to inflammation.The study found that the protein of OMP25 has cytotoxic, can lead to inflammation interact with host cytokine FTH1, but the regulation mechanism of the MAPK signaling pathway induced inflammatory response is unclear.This research project:①construct brucella Virulent strain 2308 omp25 gene deletion strains△omp25;②Determine significant differences cytokines by omp25 gene deletion strains△omp25 and Virulent strain 2308 stimulate cell;③Screen and identify MAPK signaling pathway that interaction with OMP25 and FTH1，and find its founction;④Detect differential expression of omp25 gene deletion strains△omp25 and Virulent strain 2308 of the MAPK signaling pathway during infection by in vivo and in vitro tests then analysis of Brucella OMP25 protein activated MAPK in the process of infection and inflammation mechanisms and biological effects,provide a theoretical basis to reveal the mechanism of inflammation and Brucella pathogenesis.

丝裂原活化蛋白激酶(MAPK)是体内重要的信号转导通路之一，能被多种炎性刺激所激活，对炎症的发生、发展起重要调控作用。布鲁氏菌外膜蛋白OMP25是炎症相关因子，在国家自然基金的资助下，研究发现OMP25蛋白具有细胞毒性，能引发细胞的炎症反应，并与宿主因子FTH1发生相互作用，但其如何调控MAPK信号通路诱发炎症反应的机制尚不清楚。本项目研究以①构建布鲁氏菌2308标准株omp25基因缺失株△omp25；②确定△omp25和2308标准株刺激细胞分泌量差异显著的细胞因子；③筛选并鉴定与OMP25和FTH1发生互作的MAPK信号通路的分子，验证其功能；④体内试验检测△omp25和2308标准株在感染过程中MAPK信号通路各要素的表达差异为主要研究内容，比较分析布鲁氏菌OMP25蛋白在感染和炎症反应过程中激活MAPK的机制及其生物学效应，为揭示炎症发生机理和布鲁氏菌致病机制提供科学依据。

构建并获得布鲁氏菌国际标准强毒株2308株omp25基因缺失突变株△omp25，确定△omp25和2308标准株刺激胚胎滋养层细胞分泌量差异显著的细胞因子TNF-α；发现了布鲁氏菌外膜蛋白OMP25在感染过程中发生作用的MAPK信号通路支路P38支路，初步阐明了布鲁氏菌感染细胞和个体致炎过程中OMP25的调控机制。培养博士研究生3名，培养硕士研究生4名。发表SCI收录论文5篇，国内核心期刊论文4篇。超额完成了既定的研究任务和目标。