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

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (2): 145-149.

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

阳帆, 李坚, 谷彬, 赵文健, 杨志英

湘南学院基础医学部病原生物学及免疫学教研室,郴州 423000,湖南

收稿日期:2012-12-12 修回日期:2014-01-08 出版日期:2014-02-26 发布日期:2014-03-31
通讯作者: 杨志英,女,教授,研究方向:抗感染免疫。Tel: 0735-2653161 E-mail: zyyang16@163.com
作者简介:阳帆,男,硕士研究生,主要从事病原生物学研究。Tel: 0735-2653161 E-mail: yachvili@aliyun.com
基金资助:
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。

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

YANG Fan, LI Jian, GU Bin, ZHAO Wen-jian, YANG Zhi-ying

Department of Microbiology and Immunology, Xiang Nan College of Medicine Department of Basic Medicine,Chenzhou 423000, Hunan, China

Received:2012-12-12 Revised:2014-01-08 Online:2014-02-26 Published:2014-03-31

摘要/Abstract

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 10 mg/L TEL孵育 6 h 预处理细胞,随后加入不同浓度NTHi孵育3～9 h,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-κB和活化蛋白(Activator protein-1,AP-1)DNA结合活性。结果: NTHi能明显诱导NCI-H292细胞产生和表达MUC5AC,并能激活NF-κB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NF-κB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-1 DNA结合活性有关。

关键词: 不可分型流感嗜血杆菌, 泰利霉素, AP-1, NF-κB, MUC5AC

Abstract: AIM: To investigate the effect of Telithromycin on nontypeable Haemophilus influenza (NTHi)-induced mucus MUC5AC expression in airway epithelial cells and underlying molecule mechanism.METHODS: Cultured NCI-H292 cells were pre-incubated with 10 mg/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-κB and activator protein-1 (AP-1) were detected by ELISA.RESULTS: NTHi significantly increased MUC5AC gene and protein expression in NCI-H292 cells, and it could activate NF-κB and AP-1. Telithromycin significantly attenuated NTHi-induced MUC5AC mRNA and protein expression, and inhibit AP-1 activation as well, but not NF-κB.CONCLUSION: Telithromycin can attenuate NTHi-induced mucus expression via inhibition of AP-1 but not NF-κB.

Key words: nontypeable haemophilus influenzae, telithromycin, activator protein-1, NF-κB, MUC5AC

中图分类号:

R965.2

阳帆, 李坚, 谷彬, 赵文健, 杨志英. 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[J]. 中国临床药理学与治疗学, 2014, 19(2): 145-149.

YANG Fan, LI Jian, GU Bin, ZHAO Wen-jian, YANG Zhi-ying. Telithromycin suppresses nontypeable Haemophilus influenzae-induced MUC5AC expression via inhibition of activator protein-1 signaling[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(2): 145-149.

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