鹦鹉热嗜衣原体蛋白CPSIT_0271通过激活MAPK信号通路诱导宿主细胞炎症反应及机制研究

项目名称： 鹦鹉热嗜衣原体蛋白CPSIT_0271通过激活MAPK信号通路诱导宿主细胞炎症反应及机制研究

项目编号： No.81202323

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学免疫学、法医学

项目作者： 贺庆芝

作者单位： 南华大学

项目金额： 23万元

中文摘要： 鹦鹉热嗜衣原体（Cps）感染可引起肺炎、淋巴瘤等多种疾病，炎症反应过度导致免疫性损伤是Cps致病的关键，但机制尚未明确。本课题组的前期研究结果表明CPSIT_0271能诱导Hela细胞产生IL-1β等炎症因子，并上调磷酸化p38蛋白。结合国内外文献报道，我们提出如下科学假说：Cps通过T3SS分泌CPSIT_0271，激活MAPK信号通路，发挥促炎症作用。本研究拟建立相关受体和信号通路关键分子的细胞转染模型，采用RNA干扰技术沉默MyD88基因和特异性化学抑制剂INF007、SB203580、U0126、SP600125阻断T3SS、p38、ERK、JNK信号分子，研究MAPK信号通路对CPSIT_0271诱导炎症因子的影响，阐明CPSIT_0271致炎症反应的信号转导与调控的分子机制。本项目的完成不仅能丰富Cps致炎症反应的新理论和新知识，而且能为Cps临床新的抗炎药物的研制提供新思路。

中文关键词： 鹦鹉热嗜衣原体；T3SS；INP0007；MAPK；炎症

英文摘要： Chlamydophila psittaci(Cps), an obligate intracellular bacterial parasite, can lead to many diseases such as pneumonia, rthritis, lymphoma and so on. Chlamydial infection is characterized by inflammation which, exacerbated by reinfection, ultimately leads to tissue damage and scarring. Chlamydial interaction with the cytokine system is thus likely to be central to disease, while the molecular mechanism is not well-documented. Our previous results showed that CPSIT_0271 protein could induce the expression of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8), and upregulate the phosphorylated p38 protein. According to the academic reports or thesis both at home and abroad, we postulate that effector protein CPSIT_0271 induce inflammatory response by TLR2-mediated MAPK signaling pathway. To prove this thesis statement, cell transfection about related receptor and key molecules of cell signaling pathways should be performed. The cells will be pretreated with MyD88 RNAi or specific chemical inhibitors of T3SS (INF007), P38 MAPK (SB203580), ERK (U0126), and JNK (SP600125), followed by CPSIT_0271 protein treatment. The levels of inflammatory factor, including IL-1β, IL-6, TNF-α and IL-8, will be detected with quantitative real time polymerase chain reaction (

英文关键词： Chlamydophila psittaci；T3SS；INP0007；MAPK；inflammation