鼻咽癌细胞5-8F通过TLR4介导的信号通路对革兰氏阴性细菌脂多糖的反应性研究  

The Study of Nasopharygeal Carcinoma Cell 5-8F Responsiveness to Negative Gram's Lipopolysaccharide via TLR4-regulating Signaling Pathway

作　　者：杨一新[1] 杨云波[2] 周鸣[3] 周后德[3] 向波[3] 彭淑平[3] 李小玲[3] 沈守荣[4] 李桂源[3] 

机构地区：[1]广州医学院生物化学教研室,广州510082 [2]中南大学药学院,长沙410078 [3]中南大学肿瘤研究所,长沙410078 [4]中南大学湘雅三医院,长沙410078

出　　处：《生物化学与生物物理进展》2007年第2期138-145,共8页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金资助项目(30300201;30470955;30330560)~~

摘　　要：鼻咽上皮细胞无时无刻不暴露和接触到共生微生物与病原微生物,机体依靠天然防御系统和抗原识别的适应性免疫反应系统来进行自我保护.慢性感染的重要毒力因素被认为是革兰氏阴性细菌细胞壁的主要成分脂多糖(LPS),对LPS的识别与信号传导是宿主细胞抵御革兰氏阴性细菌的关键.通过流式细胞术、RT-PCR等研究发现,5-8F细胞可与LPS相结合并产生反应,且其受LPS调节的机制是由于5-8F细胞中存在LPS受体分子如CD14、TLR4与MD2等的表达.同时应用免疫荧光、蛋白质印迹、荧光素酶报告系统等研究发现,5-8F细胞可受到LPS的诱导而活化TLR4的下游信号传导通路.5-8F细胞在LPS的诱导下,磷酸化NFκBp65的表达增加,并且使NFκBp65活化迁移至核内.研究还发现,LPS增加TNF-α全长启动子活性,同时LPS可使5-8F细胞中TNF-α的分泌增加,从而介导炎性因子的释放.因此,5-8F细胞可通过与LPS受体分子:CD14、TLR4及MD2与LPS相结合并反应,从而激活TLR4介导的NFκB信号通路,使炎性因子的释放增加,导致鼻咽部的炎症反应诱发鼻咽癌.Nasopharynx epithelial cells are constantly exposed to both commensal and pathogenic micro-organisms. After being stimulated by some microbial, the nasopharynx epithelial cells secrete a lot of inflammatory factors that lead to the inflammation of nasopharynx and further result in the nasopharyngeal carcinoma and other disorders. LPS is the most important commensal or pathogenic bacteria constituents. It is related to the pathogenesis of a variety of disease. It has been shown that the 5-8F cells could bind with the FITC-labeling LPS for its expression of CD14, TLR4 and MD2 with flow cytometry and RT-PCR assay. With immunofluoresense, Western-blot and luciferase reporter system assay, it is indicated that LPS activated the TLR4 signaling pathway in 5-8F cells. Phospho-NFκB p65 expression was increased and entered into the nuclear in 5-8F cells with LPS inducement. Furthermore, after LPS stimulation, TNF-α promoter activity and the relevant amount of TNF-α being produced were increased in 5-8F cells. In conclusion, 5-8F cells expressed CD14, TLR4 and MD2 that are crucial for LPS binding. When nasophamyx epithelial cells were induced by LPS, they did respond to LPS via TLR4 signaling pathways and activated NFr, B signaling pathway, which can further lead to nasophamyx inflammation and other nasophamyx disorders.

关 键 词：脂多糖 鼻咽癌细胞系 TOLL受体 信号传导通路 

分 类 号：R363.1[医药卫生—病理学] R392.1[医药卫生—基础医学]