Administration of mycobacterial Ag85A and IL-17A fusion protein attenuates airway inflammation in a murine model of asthma
Administration of mycobacterial Ag85A and IL-17A fusion protein attenuates airway inflammation in a murine model of asthma
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DOI：
10.1016/j.intimp.2013.10.009
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发表时间：
2013-12-01
影响因子：
5.6
通讯作者：
Zhang, Jian-hua
中科院分区：
文献类型：
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作者：
Jin, Rong;Guo, Sheng;Zhang, Jian-hua
白细胞介素(IL)-17A有助于哮喘的发展，特别是在气道中性粒细胞浸润的严重哮喘中。然而，il - 17a阻断抗体在小鼠模型中可升高T辅助（Th） 2细胞因子，如IL-13、IL-4。我们旨在确定分枝杆菌Ag85A和IL-17A融合蛋白-Ag85A-1L-17A对小鼠哮喘模型气道炎症的影响。构建、表达并纯化了融合分枝杆菌免疫优势抗原Ag85A的IL-17A重组蛋白。将融合蛋白注入BALB/c小鼠，在小鼠哮喘模型中观察其对炎症细胞浸润、BALF中Th2/Th17细胞因子、肺组织组织病理学改变及肺组织趋化因子的抗炎作用。我们发现，分枝杆菌Ag85A和IL-17A融合蛋白可诱导血清中IL-17A特异性免疫球蛋白（Ig）G，并显著降低支气管肺泡灌洗液（BALF）中IL-17A和IL-6的水平。接种Ag85A-IL-17A后，小鼠细支气管周围炎症细胞浸润明显减少，BALF总细胞、嗜酸性粒细胞和中性粒细胞明显减少。Ag85A-IL-17A可显著降低卵清蛋白致敏小鼠BALF中IL-13和IL-4水平的升高，同时免疫Ag85A-IL-17A组肺组织中CD3+CD4+IL-13（+）脾细胞受OVA刺激及CXCL1 mRNA、CCl2 mRNA和GATA-3 mRNA表达明显降低。结果表明，Ag85A-IL-17A在小鼠哮喘模型中具有显著的抗过敏作用，可能对过敏性哮喘具有保护作用。(C) 2013 Elsevier B.V.版权所有
Interleukin (IL)-17A contributes to the development of asthma, especially in severe asthma which has characteristic neutrophil infiltration in airways. However, IL-17A-blocking antibody could escalate T helper (Th) 2 cytokines, such as IL-13, IL-4 in murine models. We aimed at determining the effect of mycobacterial Ag85A and IL-17A fusion protein -Ag85A-1L-17A on airway inflammation in a murine model of asthma. IL-17A recombinant protein fused mycobacterial immunodominant antigen Ag85A was constructed, expressed and purified. The fusion protein was then administrated into BALB/c mice and its anti-inflammatory effects in the infiltration of inflammatory cells, Th2/Th17 cytokines in BALF, histopathological changes of lung tissues as well as chemokines in lung tissues were evaluated in the murine model of asthma. We found that administration of mycobacterial Ag85A and IL-17A fusion protein induced IL-17A specific immunoglobulin (Ig)G in sera and significantly decreased IL-17A and IL-6 levels in bronchoalveolar lavage fluid (BALF). Ag85A-IL-17A vaccinated mice also showed marked reduction in the infiltration of inflammatory cells in peribronchiolar region and significant decrease in total cells, eosinophil cells and neutrophil cells in BALF. The increased levels of IL-13 and IL-4 in BALF of ovalbumin-sensitized mice were significantly reduced by the administration of Ag85A-IL-17A Furthermore, CD3+CD4+IL-13(+) splenocytes stimulated with OVA and CXCL1 mRNA, CCl2 mRNA and GATA-3 mRNA expressed in lung tissues were decreased markedly in Ag85A-IL-17A vaccinated group. Our results demonstrate remarkable antiallergic effects of Ag85A-IL-17A in a murine model of asthma and it may have protective effects on allergic asthma. (C) 2013 Elsevier B.V. All rights reserved.