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首页> 外文期刊>Allergy >A potential new target for asthma therapy: a disintegrin and metalloprotease 10 (ADAM10) involvement in murine experimental asthma.
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A potential new target for asthma therapy: a disintegrin and metalloprotease 10 (ADAM10) involvement in murine experimental asthma.

机译：哮喘治疗的潜在新目标：整合素和金属蛋白酶10（ADAM10）参与鼠类实验性哮喘。

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BACKGROUND: Elevated levels of CD23, a natural regulator of IgE production, have been shown to decrease the signs of lung inflammation in mice. The aim of this study was to study the involvement of ADAM10, the primary CD23 sheddase, in experimental asthma. METHODS: ADAM10 was blocked either by using mice with a B-cell-specific deletion of the protease or pharmacologically by intranasal administration of selective ADAM10 inhibitors. Airway hypersensitivity (AHR) and bronchoaveolar lavage fluid (BALF) eosinophilia and select BALF cytokine/chemokine levels were then determined. RESULTS: Using an IgE and mast cell-dependent mouse model, B-cell-specific ADAM10(-/-) mice (C57B/6 background) exhibited decreased eosinophilia and AHR when compared with littermate (LM) controls. Treatment of C57B/6 mice with selective inhibitors of ADAM10 resulted in an even further decrease in BALF eosinophilia, as compared with the ADAM10(-/-) animals. Even in the Th2 selective strain, Balb/c, BALF eosinophilia was reduced from 60% to 23% respectively. In contrast, when an IgE/mast cell-independent model of lung inflammation was used, the B-cell ADAM10(-/-) animals and ADAM10 inhibitor treated animals had lung inflammation levels that were similar to the controls. CONCLUSIONS: These results thus show that ADAM10 is important in the progression of IgE-dependent lung inflammation. The use of the inhibitor further suggested that ADAM10 was important for maintaining Th2 levels in the lung. These results thus suggest that decreasing ADAM10 activity could be beneficial in controlling asthma and possibly other IgE-dependent diseases.
机译：背景：已经证明，升高水平的CD23是IgE产生的天然调节剂，可减少小鼠肺部炎症的迹象。这项研究的目的是研究ADAM10（主要的CD23脱氢酶）与实验性哮喘的关系。方法：通过使用具有B细胞特异性蛋白酶缺失的小鼠或通过鼻内给药选择性ADAM10抑制剂的药理作用来阻断ADAM10。然后确定气道超敏反应（AHR）和支气管肺灌洗液（BALF）嗜酸性粒细胞增多，并选择BALF细胞因子/趋化因子水平。结果：使用IgE和肥大细胞依赖性小鼠模型，B细胞特异性ADAM10（-/-）小鼠（C57B / 6背景）与同窝幼仔（LM）对照相比，表现出降低的嗜酸性粒细胞和AHR。与ADAM10（-/-）动物相比，用ADAM10的选择性抑制剂治疗C57B / 6小鼠导致BALF嗜酸性粒细胞减少甚至更多。即使在Th2选择性菌株Balb / c中，BALF嗜酸性粒细胞减少也分别从60％降至23％。相反，当使用不依赖IgE /肥大细胞的肺部炎症模型时，B细胞ADAM10（-/-）动物和ADAM10抑制剂治疗的动物的肺部炎症水平与对照组相似。结论：因此，这些结果表明ADAM10在IgE依赖性肺部炎症的进展中很重要。使用抑制剂进一步表明，ADAM10对于维持肺中Th2水平很重要。因此，这些结果表明，降低ADAM10活性可能有利于控制哮喘和其他可能依赖IgE的疾病。

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