HSP70/CD80 DNA疫苗通过调节Th1/Th2/Treg/Th17细胞对小鼠急性哮喘的抑制作用

doi:10.6040/j.issn.1671-7554.0.2014.284

山东大学学报（医学版） ›› 2014, Vol. 52 ›› Issue (10): 20-24.doi: 10.6040/j.issn.1671-7554.0.2014.284

HSP70/CD80 DNA疫苗通过调节Th1/Th2/Treg/Th17细胞对小鼠急性哮喘的抑制作用

李燕¹, 谢敏², 史小玲¹, 王晓燕¹, 唐利¹, 钟森³, 陈庄¹

1. 泸州医学院附属医院医学实验中心, 四川泸州 646000;
2. 成都华西海圻医药科技有限公司, 四川成都 610041;
3. 成都中医药大学附属医院, 四川成都 610075

收稿日期:2014-05-04 修回日期:2014-09-19 出版日期:2014-10-10 发布日期:2014-10-10
通讯作者: 陈庄。E-mail：chen917744799@qq.com E-mail:chen917744799@qq.com
基金资助:
四川省科技厅科技支撑计划（2011SZ0015）；四川省科技厅应用基础研究项目（2009JY0076）

Hsp70/CD80 DNA vaccine inhibits asthma by regulating the balance of Th1/Th2/Treg/Th17 in an acute mouse model

LI Yan¹, XIE Min², SHI Xiaoling¹, WANG Xiaoyan¹, TANG Li¹, ZHONG Sen³, CHEN Zhuang¹

1. Molecular Medicine Experimental Center, Affiliated Hospital of Luzhou Medicine College, Luzhou 646000, Sichuan, China;
2. WestChina-Frontier Pharmaceutical Technology Company, Chengdu 610041, Sichuan, China;
3. Affiliated Hospital of Chengdu University of TCM, Chengdu 610075, Sichuan, China

Received:2014-05-04 Revised:2014-09-19 Online:2014-10-10 Published:2014-10-10

摘要/Abstract

摘要： 目的考察热休克蛋白70（HSP70）/CD80 DNA疫苗治疗小鼠急性哮喘的疗效，研究该过程中Th1/Th2/Treg/Th17再平衡的作用机制。方法 BALB/c小鼠40只随机分为空白对照组（空白组），哮喘模型组（模型组），pVAX1（+）空载体对照组（空载组）和HSP70/CD80疫苗治疗组（治疗组），每组10只。鸡卵清蛋白（OVA）激发致敏小鼠构建急性哮喘模型，HSP70/CD80 DNA疫苗进行治疗。吸入性支气管激发试验测定气道反应性，ELISA法测定血清中IgE的含量，HE和AB-PAS染色观察肺组织病理学改变，ELISA法观察支气管肺泡灌洗液中γ-干扰素（IFN-γ）、白细胞介素-4（IL-4）、转化生长因子β（TGF-β）和白细胞介素-17（IL-17）等细胞因子的含量变化，实时荧光定量PCR观察肺组织中T-bet、GATA连接蛋白3（GATA-3）、叉头蛋白3（Foxp3）和维甲酸受体相关孤儿受体（RORγt）等转录因子的表达。结果与模型组相比，DNA疫苗治疗后小鼠气道反应性明显下降（P<0.05），IgE浓度降低（P<0.05），肺组织炎症浸润减少，杯状细胞增生不明显，IFN-γ/IL-4和TGF-β/IL-17比值升高（P均<0.05），T-bet/GATA-3和Foxp3 /RORγt比值升高（P均<0.05）。结论 HSP70/CD80 DNA疫苗可能通过改变IFN-γ/IL-4和TGF-β/IL-17的比值、T-bet/GATA-3和Foxp3/RORγt的比值，使Th1/Th2/Treg/Th17恢复平衡，从而发挥对哮喘的治疗作用。

关键词: CD4+CD25+调节性T细胞, 辅助性T细胞17, 哮喘

Abstract: Objective To explore the mechanism of Th1/Th2/Treg/Th17 rebalance in an acute asthma mouse model treated with heat shock protein70 (Hsp70)/CD80 DNA vaccine. Methods Forty BALB/c mice were divided into the control group, asthma-model group, pVXA1-vector group and vaccine treatment group, 10 in each group. They were intraperitoneally injected into ovalbumin (OVA) to build acute asthma model and treated with DNA vaccine. The airway responsiveness was evaluated after inhaling the methacholine(Mch). The IgE content in serum was detected by ELISA. The pathological change of lung tissue was observed by HE and AB-PAS staining. The expressions of interferon-γ(IFN-γ), interleukin-4 (IL-4), ransforming growth factor beta (TGF-β) and interleukin-17 (IL-17) in BALF were measured by ELISA. The expressions of T-bet, GATA binding protein 3 (GATA-3), forkheah box protein3 (Foxp3) and retinoid related orphan receptor gamma t (RORγt) in lung tissue were detected by Real-time PCR. Results Compared with asthmatic mouse, mouse treated with vaccine exhibited the decreased airway responsiveness, IgE (all P<0.05) and inflammatory infiltration of lung tissues, repressed proliferation of goblet cells, and increased IFN-γ/IL-4, TGF-β/IL-17, T-bet/GATA-3 and Foxp3/RORγt (all P<0.05). Conclusion The Hsp70/CD80 DNA vaccine plays a therapeutic role in asthma by restoring the balance of Th1/Th2/Treg/Th17 cell.

Key words: CD4+CD25+ Regulatory T cell, T helper cell 17, Asthma

中图分类号:

R392.9

李燕, 谢敏, 史小玲, 王晓燕, 唐利, 钟森, 陈庄. HSP70/CD80 DNA疫苗通过调节Th1/Th2/Treg/Th17细胞对小鼠急性哮喘的抑制作用[J]. 山东大学学报（医学版）, 2014, 52(10): 20-24.

LI Yan, XIE Min, SHI Xiaoling, WANG Xiaoyan, TANG Li, ZHONG Sen, CHEN Zhuang. Hsp70/CD80 DNA vaccine inhibits asthma by regulating the balance of Th1/Th2/Treg/Th17 in an acute mouse model[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(10): 20-24.

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HSP70/CD80 DNA疫苗通过调节Th1/Th2/Treg/Th17细胞对小鼠急性哮喘的抑制作用

Hsp70/CD80 DNA vaccine inhibits asthma by regulating the balance of Th1/Th2/Treg/Th17 in an acute mouse model

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