固有免疫细胞表面的TLR会识别细菌的脂多糖（LPS）等，活化NF-kB并产生大量炎症因子，而对该信号通路调控机制的研究并不完善。我们前期研究发现，LPS刺激巨噬细胞后，E3连接酶TRIP的表达量明显增加，对TRIP特异性的干扰可显著增强LPS诱导的TNF-α、IL-6的表达，进一步研究显示，TRIP可与磷酸激酶TAK1发生结合，并促进其降解。我们提出假设，TRIP可能会作为E3泛素连接酶将TAK1进行K48位泛素化并使其降解，进而负向调控TLR4介导的炎症反应。本研究利用内毒素休克模型和RT-PCR、报告基因、免疫共沉淀、体外泛素化等分子技术手段证明这一假说。本研究旨在阐明TRIP调节TLR4介导的炎症反应的分子机制，为TLR4信号转导机制提供新的认识；探讨TRIP可否作为反馈信号调节TNF-α、IL-6的产生，为寻找基因转染防治细菌感染及内毒素休克等疾病提供理论基础。

Innate immunity is the first line to defense against pathogenic microorganisms, lipopolysaccharide on surface of bacteria is recognized by TLR4, then produce large amounts of inflammatory cytokines, such as TNF-α and IL-6. But the study on the mechanism of this pathway is not perfect. Our previous study found that the expression of E3 ligase TRIP increased significantly when macrophages was stimulated by LPS; the specific interference to the TRIP can significantly increase the expression of TNF- α, IL-6 induced by LPS. further research shows, TRIP could combine with phosphokinase TAK1, then promote its degradation. The endotoxin-shock model, RT-PCR, report gene, Co-immunoprecipitation, in vitro ubiquitination and other molecular techniques will be used to systematically investigate the influence of TRIP on TLR4 mediated TNF- α, IL-6 production and TAK1 ubiquitination. The purpose of this study was to elucidate the TRIP function in inflammatory reaction mediated by TLR4, and provide new insight into the TLR4 signal transduction mechanism; To investigate the expression of TRIP can be used as feedback signal regulation of TNF- α, IL-6 production, it will also provide a new way for preventing bacterial infections, endotoxin shock and other ills .