泰利霉素经AP-1途径抑制不可分型流感嗜血杆菌诱导的MUC5AC表达  

Telithromycin suppresses nontypeable Haemophilus influenzae-induced MUC5AC expression via inhibition of activator protein-1 signaling

作　　者：阳帆[1] 李坚[1] 谷彬[1] 赵文健[1] 杨志英[1] 

机构地区：[1]湘南学院基础医学部病原生物学及免疫学教研室

出　　处：《中国临床药理学与治疗学》2014年第2期145-149,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：湖南教育厅计划项目(09C912);湘南学院"十二五"重点学科免疫学资助

摘　　要：目的：研究大环内酯类抗生素泰利霉素（telithromycin，TEL）对不可分型流感嗜血杆菌（nontypeable haemophilus influenzae，NTHi）诱导气道上皮细胞表达黏蛋白MUC5AC的影响，并探讨其可能的分子机制。方法：体外培养NCI-H292细胞，用10mg／LTEL孵育6h预处理细胞，随后加入不同浓度NTHi孵育3～9h，分别采用ELISA和实时定量PCR检测MUC5AC蛋白和mRNA的表达情况，ELISA检测NCI-H292细胞内NF-KB和活化蛋白（Activa-torprotein-1，AP-1）DNA结合活性。结果：NT-Hi能明显诱导NCI-H292细胞产生和表达MUC5AC，并能激活NF-IcB和AP-1。而TEL处理后，能明显抑制NTHi诱导的MUC5AC蛋白和mRNA表达，并有效抑制AP-1的DNA结合活性，但对N1a-KB活性无明显影响。结论：TEL能抑制NTHi诱导的黏蛋白表达，其机制可能与抑制AP-1DNA结合活性有关。To investigate the effect of Telithromycin on nontypeable Haemophilus in fluenza （NTHi）-induced mucus MUC5AC ex pression in airway epithelial cells and underlying molecule mechanism. METHODS ： Cultured NCI-H292 cells were pre-incubated with 10 rag/ L of Telithromycin for 6 h, and then NTHi was added in different concentrations for 3- 9 h. MUC5AC gene mRNA level and mucin protein expression were quantified by real time PCR and ELISA, respectively; DNA-binding activities of NF-~B and activator protein-1 （AP-1） were de tected by ELISA. RESULTS：NTHi significantlyincreased MUCSAC gene and protein expression in NCI-H292 cells, and it could activate NF-kB and AP-1. Telithromycin significantly attenua- ted NTHi-induced MUC5AC mRNA and protein expression, and inhibit AP-1 activation as well, but not NF-kB. CONCLUSION： Telithromycin can attenuate NTHi-induced mucus expression via inhibition of AP-1 but not NF-kB.

关 键 词：不可分型流感嗜血杆菌 泰利霉素 AP-1 NF-xB MUC5AC 

分 类 号：R965.2[医药卫生—药理学]