JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2014, Vol. 52 ›› Issue (10): 20-24.doi: 10.6040/j.issn.1671-7554.0.2014.284

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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. 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

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

CLC Number: 

  • R392.9
[1] Pelaia G, Vatrella A, Maselli R. The potential of biologics for the treatment of asthma[J]. Nat Rev Drug Discov, 2012, 11(12): 958-972.
[2] 成争艳, 史小玲, 何光彤, 等.热休克蛋白70/CD80嵌合疫苗对支气管哮喘小鼠的影响[J].中华结核和呼吸杂志, 2009, 32(9):716-717.
[3] 李燕, 郭宇, 史小玲, 等. HSP70/CD80 DNA疫苗通过调节趋化因子及受体对哮喘小鼠气道炎症的作用[J]. 中华微生物学与免疫学杂志, 2013, 33(2): 123-128. LI Yan, GUO Yu, SHI Xiaoling, et al. The effect of HSP70/CD80 DNA vaccine on airway inflammation by regulating the chemokine and the receptor of chemokine in asthmatic mice[J]. Chin J Microbiol Immunol, 2013, 33(2):123-128.
[4] 李晖, 史小玲, 钟森, 等.hsp70/CD80嵌合DNA真核表达质粒的构建及鉴定[J].中华结核和呼吸杂志, 2002, 25(4): 244-245.
[5] Tanaka H, Masuda T, Tokuoka S, et al. The effect of allergen-induced airway inflammation on airway remodeling in a murine model of allergic asthma[J]. Inflamm Res, 2001, 50(12): 616-624.
[6] McMillan S J, Xanthou G, Lloyd C M. Manipulation of allergen-induced airway remodeling by treatment with anti-TGF-beta antibody: effect on the Smad signaling pathway[J]. J Immunol, 2005, 174(9): 5774-5780.
[7] Wakashin H, Hirose K, Maezawa Y, et al. IL-23 and Th17 cells enhance Th2-cell-mediated eosinophilic airway inflammation in mice[J]. Am J Respir Crit Care Med, 2008, 178(10): 1023-1032.
[8] Wachstein J, Tischer S, Figueiredo C, et al. HSP70 enhances immunosuppressive function of CD4(+)CD25(+)FoxP3(+) T regulatory cells and cytotoxicity in CD4(+)CD25(-) T cells[J]. PLoS One, 2012, 7(12): 51747-51777.
[9] Barnes M J, Griseri T, Johnson A M, et al. CTLA-4 promotes Foxp3 induction and regulatory T cell accumulation in the intestinal lamina propria[J]. Mucosal Immunol, 2013, 6(2): 324-334.
[10] Bouguermouh S, Fortin G, Baba N, et al. CD28 co-stimulation down regulates Th17 development[J]. PLoS One, 2009, 4(3): 5087-5117.
[11] Maier E, Duschl A, Horejs-Hoeck J. STAT6-dependent and -independent mechanisms in Th2 polarization[J]. Eur J Immunol, 2012, 42(11): 2827-2833.
[12] Lohoff M, Mak T W. Roles of interferon-regulatory factors in T-helper-cell differentiation[J]. Nat Rev Immunol, 2005, 5(2): 125-135.
[13] Oestreich K J, Weinmann A S. T-bet employs diverse regulatory mechanisms to repress transcription[J]. Trends Immunol, 2012, 33 (2): 78-83.
[14] Oboki K, Ohno T, Saito H, et al. Th17 and allergy[J]. Allergol Int, 2008, 57(2): 121-134.
[15] 李洧, 叶茜, 高顺翠, 等. 白细胞介素17抗体对哮喘小鼠中性粒细胞的影响[J]. 山东大学学报:医学版, 2009, 47(3): 43-47. LI Wei, YE Qian, GAO Shuncui, et al. Effects of IL-17 neutralization antibody on polymorph-nuclear of asthma in mice[J]. Journal of Shandong University: Health Sciences, 2009, 47(3): 43-47.
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