哮喘患者气道上皮TSLP表达加重气道炎症的研究  

Expression of thymic stromal lymphopoietin promotes airway inflammation in asthmatic patients

作　　者：亓慧娟[1,2] 李艳丽[1] 吴金香[1] 谢淑奇[1] 李鸿佳[3] 王晓平[3] 刘方平 王荣[4] 董亮[1] 

机构地区：[1]山东大学齐鲁医院呼吸内科,济南250012 [2]山东省禹城市人民医院呼吸科,山东禹城251200 [3]山东省胸科医院呼吸科,济南250013 [4]山东大学教育部卫生部心血管重构与功能研究重点实验室,济南250012

出　　处：《山东大学学报（医学版）》2011年第12期143-148,共6页Journal of Shandong University:Health Sciences

摘　　要：目的研究支气管哮喘患者气道上皮中胸腺基质淋巴细胞生成素(TSLP)的表达,探讨其对哮喘患者气道炎症的影响。方法采用免疫荧光法测定哮喘患者(哮喘组)及健康人(对照组)各10例支气管镜刷检涂片中TSLP的表达活性,酶联免疫吸附试验(ELISA)检测肺泡灌洗液(BALF)中TSLP含量及血浆中白细胞介素4(IL-4)、白细胞介素5(IL-5)和白细胞介素13(IL-13)的含量,流式细胞术检测外周血单个核细胞(PBMCs)中CD40、CD80、CD86的表达水平。结果哮喘组血浆中IL-4、IL-5和IL-13的水平显著高于对照组(P<0.05),且TSLP与其成正相关;与对照组相比,哮喘组气道上皮TSLP,PBMCs中CD40、CD80、CD86高表达(P均<0.01);吸入舒利迭(50/250)治疗1个月后,气道上皮TSLP,PBMC中CD40、CD80、CD86的表达水平明显降低,血浆中TSLP、IL-4、IL-5和IL-13的含量也降低。结论哮喘气道上皮中TSLP表达增高,TSLP通过上调CD40、CD80、CD86表达,激活树突状细胞(DC)诱导CD 4+T细胞向Th2分化发育,加重哮喘的气道炎症,通过降低TSLP表达可降低DC的活化,减少Th2细胞因子的分泌,从而减轻哮喘炎症反应,为哮喘提供新的治疗途径。Objective To study expression of thymic stromal lymphopoietin（TSLP） and activation of dendritic cells（DC） in airway epithelia of asthmatic patients,and to investigate the effect and underlying mechanism of TSLP on airway inflammation.Methods 10 asthmatic patients（asthma group） and 10 healthy subjects（control group） were collected.Bronchoscopic brushing smears were implemented to determine expression of TSLP by immunofluorescence cytochemistry.The levels of TSLP,IL-4,IL-5 and IL-13 were detected by enzyme-linked mmunosorbent assay（ELISA）.Expressions of CD40,CD80 and CD86 in peripheral blood mononuclear cells（PBMCs） were detected by florescence-activated cell sorting（FACS）.Results IL-4,IL-5 and IL-13 levels in the plasma in the asthma group were significantly higher than those in the control group（P0.05）.Tight correlations of TSLP with IL-4,IL-5 and IL-13 were identified.TSLP in airway epithelia in the asthma group was more significantly increased compared with the control group（P0.01）.Expressions of CD40,CD80 and CD86 in PBMCs in the asthma group were significantly higher than in the control group（P0.01）.After treatment with inhalation of seretide（50/250） for one month,expression of TSLP and in asthmatic airway epithelia levels of CD40,CD80 and CD86 in PBMCs were significantly decreased,and levels of IL-4,IL-5 and IL-13 in the plasma were also reduced.Conclusion TSLP is highly expressed in bronchial epithelia of asthmatic patients.TSLP activates DC by up-regulating expressions of CD40,CD80 and CD86,which induces CD＋4 T cells to differentiate into Th2 cells and to produce type 2 responses,so that airway inflammation of asthma is aggravated.Activation of DC can be decreased by reducing expression of TSLP and secretion of Th2 cytokines,thereby alleviating inflammation of asthma.TSLP provides a promising strategy for the treatment of asthma.

关 键 词：胸腺生成素类 白细胞介素类 树突细胞 哮喘 

分 类 号：R562.25[医药卫生—呼吸系统]