泰利霉素经NF-κB途径抑制铜绿假单胞菌诱导MUC5AC表达  

Telithromycin suppresses Pseudomonas aeruginosa- induced MUC5AC expression via inhibition of NF-κB

作　　者：李波[1] 罗金花[1] 阳帆[2] 

机构地区：[1]南华大学附属第三医院感染科,湖南衡阳421000 [2]湘南学院基础医学部病原生物学及免疫学教研室,湖南郴州423000

出　　处：《中国当代医药》2013年第34期7-9,12,共4页China Modern Medicine

基　　金：湖南省衡阳市2012年科学技术发展项目(012KJ28)

摘　　要：目的研究大环内酯类抗生素泰利霉素（TEL）对铜绿假单胞菌（PA）诱导气道上皮细胞表达产黏蛋白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，随后加人不同浓度PA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细胞内核因子KB（NF-κB）的DNA结合活性。结果NCI—H292细胞经PA感染后6h后，MUC5AC分泌水平随PA浓度的增高而增加。此外，PA感染3h后即可检测出MUC5ACmRNA的表达，6h后达到高峰。NCI—H292细胞经TEL处理后，能显著抑制PA诱导的MUC5ACmRNA表达。PA感染NCI—H292细胞后，能促进NF-κBp50／p65亚基核转位，呈一定的时间依赖性，TEL处理后，NF-κB转录活性显著降低。结论TEL能抑制PA诱导的黏蛋白表达，其机制可能与抑制NF-κBDNA结合活性有关。Objective To investigate the effect of telithromycin（TEL）on Pseudomonas aeruginosa （PA）-induced mucus MUCSAC expression in airway epithelial cells and underlying molecule mechanism. Methods Cultured NCI-H292 ceils were pre-incubated with 10 mg/L of TEL for 6 h, and then PA was added in different concentrations.MUCSAC gene mRNA level and mucin protein expression was quantified by real time PCR and ELISA respectively; DNA- binding activities of nuclear factor κB （NF-κB）was detected by ELISA. Results After infected with PA for 6 h, secretion of MUCSAC was significantly increased as the concentration of PA increased. In addition, the MUCSAC mRNA could be detected at 3 h, and peaked at 6 h. Expression of MUCSAC mRNA was significantly decreased after TEL treatment. PA could induce NF-κB pSO/p65 subunit translocation to the nucleus in time-dependent manner, and this could also be inhibited by TEL. Conclusion TEL could attenuate PA-induced mucus expression via inhibition of the NF-κB DNA-binding activity.

关 键 词：铜绿假单胞菌 泰利霉素 核因子KB MUC5AC 

分 类 号：R966[医药卫生—药理学]