血红素加氧酶-1介导Tr1细胞在哮喘动物模型中的免疫调节作用  

Heme oxygenase-1 mediates immunoregulation of Tr1 cells in asthmatic animal model

作　　者：蔚京京[1] 钟文伟[1] 须丽清[1] 邵洁[1] 李云珠[1] 俞善昌[1] 周光炎[2] 夏振炜[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院儿科,上海200025 [2]上海市免疫学研究所,上海200025

出　　处：《临床儿科杂志》2009年第1期67-71,共5页Journal of Clinical Pediatrics

基　　金：国家自然科学基金(No.30471833,30570798);上海市科委(No.044119662);上海市教委资助项目(No.03BZ04)

摘　　要：目的探讨血红素加氧酶-1(heme oxygenase-1,HO-1)介导1型T调节细胞(type1T regulatory cells,Tr1)在哮喘动物模型中的免疫调节作用。方法用卵清蛋白(ovalbumin,OVA)致敏、激发C57B6小鼠建立哮喘模型,并在致敏、激发阶段分别经血红素(hemin)和锡-原卟啉(Sn-protoporphyrin,SnPP)干预。肺泡灌洗液细胞计数和肺脏病理组织学检测评价哮喘动物模型;real-time PCR和Western blot方法分别测定脾脏细胞内HO-1、IL-10mRNA表达和HO-1蛋白量;ELISA方法测定动物血清OVA-特异性IgE(OVA-sIgE)和IL-10水平;流式细胞计数测定脾脏细胞中CD4+CD25+IL-10+Treg、CD4+IL-10R+IFN-γR+Tr1的比例。结果哮喘小鼠模型经hemin干预后,Tr1数量增加,脾脏细胞内HO-1和IL-10mRNA表达上调,HO-1蛋白水平明显增加,血清IL-10水平增高,哮喘气道炎症减轻。结论在哮喘动物模型中HO-1可能通过诱导Tr1细胞,增加IL-10的分泌,抑制哮喘气道炎症。Objectives To explore the immunosuppressive function of type 1 T regulatory （Tr1） cells after treated with heme oxygenase-1 （HO-1） in asthmatic mouse model. Methods C57B6 mouse was sensitized and challenged by ovalbumin （OVA） and administrated with hemin or Sn-protoporphyrin （SnPP）. Airway inflammation was analyzed by cell counting of bronchoalveolar lavage fluid （BALF） and lung histopathology. The expression levels of HO-1, IL-10 mRNA and protein were detected in splenic cells. The levels of OVA-specific IgE （OVA-sIgE） and IL-10 in serum were measured by ELISA. The ratio of CD4^＋CD25^＋IL-10^＋Treg and CD4^＋IL-10R^＋IFN-γR^＋Tr1 in splenic cells was measured by flow cytometry. Results The expression levels of HO-1, IL-10 mRNA, and the products of HO-1 in splenic cells were enhanced after treated with hemin. The number of Tr1 and the concentration of serum IL-10 were increased in C57B6 mouse sensitized and challenged by OVA and hemin. Airway inflammatory severity was alleviated. Conclusions The study suggests that HO-1 suppresses asthmatic airway inflammation by enhancing the immunosuppressive function of Tr1 cells and secretion of IL-10 in asthma animal model.

关 键 词：血红素加氧酶-1 哮喘小鼠模型 调节性T细胞 IL-10 

分 类 号：R562.25[医药卫生—呼吸系统]