中国组织工程研究

中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (27): 5053-5057.doi: 10.3969/j.issn.1673-8225.2011.27.025

• 干细胞因子及调控因子 stem cell factors and regulatory factors • 上一篇    下一篇

血红素加氧酶1在间充质干细胞上调哮喘患者外周血调节性T细胞中的作用

温  冰1，颛孙永勋1，颜富德2，陈  瑞1，张  蔚1，冯素玲1，李建国1   

  1. 1中山大学孙逸仙纪念医院呼吸内科，广东省广州市  510120
    2广州市番禺区大石人民医院内科，广东省广州市  511430
  • 收稿日期:2011-01-27 修回日期:2011-05-21 出版日期:2011-07-02 发布日期:2011-07-02
  • 通讯作者: 李建国，博士，教授，硕士生导师，中山大学呼吸疾病研究所，中山大学孙逸仙纪念医院呼吸内科，广东省广州市 510120 jgli88@126.com
  • 作者简介:温冰★，女，1985年生，广东省深圳市人，汉族，中山大学孙逸仙纪念医院在读硕士，主要从事哮喘和干细胞方面的研究。 wenljh@163.com
  • 基金资助:

    广东省科技计划社会发展项目(2010B031600082)。

Hemeoxygenase-1 expression effect on the up-regulation of peripheral blood CD4+CD25+CD127low/- regulatory T cells mediated by mesenchymal stem cells in asthma patients 

Wen Bing1, Zhuansun Yong-xun1, Yan Fu-de2, Chen Rui1, Zhang Wei1, Feng Su-ling1, Li Jian-guo1   

  1. 1Department of Respiratory Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou  510120, Guangdong Province, China
    2Department of Internal Medicine, Dashi People’s Hospital, Guangzhou  511430, Guangdong Province, China
  • Received:2011-01-27 Revised:2011-05-21 Online:2011-07-02 Published:2011-07-02
  • Contact: Li Jian-guo, Doctor, Professor, Master’s supervisor, Department of Respiratory Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China jgli88@126.com
  • About author:Wen Bing★, studying for master’s degree, Department of Respiratory Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China wenljh@163.com
  • Supported by:

    the Science and Technology Program of Guangdong Province, No. 2010B031600082*

PDF

269

被引次数

6

摘要：

背景：上调CD4+CD25+CD127low/-调节性T细胞是目前治疗哮喘的新靶点。骨髓间充质干细胞在体外可上调正常人外周血的调节性T细胞，但机制尚未明确。
目的：观察血红素加氧酶1对间充质干细胞上调哮喘患者外周血CD4+CD25+CD127low/-调节性T细胞的影响。
方法：分别加入0，15，30，45，60 μmol/L氯化高铁血红素和0，5，10，15，20 μmol/L锌-原卟啉对骨髓间充质干细胞进行预处理，荧光定量PCR检测各组间充质干细胞中血红素加氧酶1 mRNA的表达量。密度梯度离心法分离哮喘急性发作期患者和健康对照者的外周血单个核细胞，分别与经氯化高铁血红素预处理、经锌-原卟啉预处理、不经预处理的间充质干细胞共孵育，加入植物血凝素反应72 h，流式细胞仪检测各组CD4+CD25+CD127low/-调节性T细胞占CD4+T细胞的比例。
结果与结论：人骨髓间充质干细胞中有血红素加氧酶1表达，其表达在体外可被诱导和抑制。间充质干细胞中血红素加氧酶1 mRNA的表达量随氯化高铁血红素浓度增加而增加(P < 0.05)，随锌-原卟啉浓度增加而减少(P < 0.05)，具有剂量依赖性。间充质干细胞在体外可提高哮喘患者和健康对照者CD4+CD25+CD127low/-调节性T细胞的水平(P < 0.01)，诱导间充质干细胞中血红素加氧酶1的表达可使共孵育后CD4+CD25+CD127low/-调节性T细胞水平提高(P < 0.01)，抑制间充质干细胞中血红素加氧酶1的表达可使共孵育后CD4+CD25+CD127low/-调节性T细胞的水平降低(P < 0.01)，但仍高于对照组(P < 0.01)。提示骨髓间充质干细胞部分通过血红素加氧酶1上调哮喘患者外周血CD4+CD25+CD127low/-调节性T细胞。

关键词: 血红素加氧酶1, 间充质干细胞, 调节性T细胞, 哮喘, 免疫调节

Abstract:

BACKGROUND: Up-regulating CD4+CD25+CD127low/- regulatory T cells is a new target in the treatment of asthma. Human bone marrow mesenchymal stem cells (MSCs) can up-regulate CD4+CD25+CD127low/- regulatory T cells in vitro, while the mechanism is not clear.
OBJECTIVE: To study the effect of hemeoxygenase-1 (HO-1) expression in the up-regulation of peripheral blood CD4+CD25+CD127low/- regulatory T cells mediated by MSCs in asthma patients.
METHODS: Real-time PCR was used to examine the expression of HO-1 mRNA in MSCs pretreated with 0, 15, 30, 45, 60 μmol/L Hemin (the revulsive of HO-1) and 0, 5, 10, 15, 20 μmol/L ZnPP (the inhibitor of HO-1) respectively. Peripheral blood mononuclear cells (PBMCs), which were isolated from 10 cases of asthma patients with acute episode and 10 cases of healthy controls using Ficoll density gradient centrifugation, were incubated with MSCs pretreated with Hemin, ZnPP and mock respectively.
RESULTS AND CONCLUSION: The expression of HO-1 in MSCs can be induced and inhibited in vitro. The higher concentration of Hemin added to MSCs, the higher expression of HO-1 mRNA was tested (P < 0.05). With the increasing concentration of ZnPP added to MSCs, the expression of HO-1 mRNA was becoming lower (P < 0.05). The proportion of CD4+CD25+CD127low/- regulatory T cells in CD4+ T cells could be up-regulated by MSCs (P < 0.01) and also by MSCs with induction of HO-1 expression (P < 0.01). While MSCs with inhibition of HO-1 expression could down-regulate the proportion of CD4+CD25+CD127low/-regulatory T cells in CD4+ T cells (P < 0.01). The expression of HO-1 partially contributed to the up-regulation of CD4+CD25+CD127low/- regulatory T cells mediated by MSCs in asthma patients.

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