Demethylallosamidin, a chitinase inhibitor, suppresses airway inflammation and hyperresponsiveness
Demethylallosamidin, a chitinase inhibitor, suppresses airway inflammation and hyperresponsiveness
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DOI：
10.1016/j.bbrc.2009.09.075
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发表时间：
2009-12-04
影响因子：
3.1
通讯作者：
Nakanishi, Yoichi
中科院分区：
文献类型：
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作者：
Matsumoto, Takafumi;Inoue, Hiromasa;Nakanishi, Yoichi
酸性哺乳动物几丁质酶响应肺部过敏原暴露而上调。我们研究了几丁质酶抑制剂别糖脒 (Allo) 和去甲基别糖脒 (Dma) 对哮喘反应的影响。将IL-13滴入小鼠气道或进行卵清蛋白致敏加上暴露，有或没有Allo或Dma治疗。评估气道高反应性（AHR）和炎症。 Allo 和 Dma 减弱了 IL-13 滴注后气道嗜酸性粒细胞增多和嗜酸性粒细胞趋化因子的上调，而 Dma（而非 Allo）抑制了 IL-13 诱导的哮喘中的 AHR。 Allo 或 Dma 将 IL-13 后 BAL 液中升高的几丁质酶活性抑制至相似水平。 IL-13 滴注后，BAL 液中的支气管保护性 PGE(2) 水平升高。 Allo（而非 Dma）抑制 IL-13 诱导的 PGE(2) 过量产生以及 COX-2 和 PGE 合成酶 1 的表达。在卵清蛋白诱发的哮喘中，Dma 比 Allo 更能抑制 AHR。这些发现表明，Dma 可减弱 IL-13 诱导的哮喘反应，而不影响 PGE(2) 合成。 Dma 可能具有作为哮喘治疗剂的潜力。 (C) 2009 Elsevier Inc. 保留所有权利。
Acidic mammalian chitinase is upregulated in response to allergen exposure in the lung. We investigated the effects of chitinase inhibitors, allosamidin (Allo) and demethylallosamidin (Dma), on asthmatic responses. Mice were subjected to IL-13 instillation into the airways or to ovalbumin sensitization plus exposure with or without treatment of Allo or Dma. Airway hyperresponsiveness (AHR) and inflammation were evaluated. Allo and Dma attenuated airway eosinophilia and the upregulation of eotaxin after IL-13 instillation, while Dma, but not Allo, Suppressed AHR in IL-13-induced asthma. Allo or Dma suppressed the elevated chitinase activity in BAL fluids after IL-13 to similar levels. The bronchoprotective PGE(2) levels in BAL fluids were elevated after IL-13 instillation. Allo, but not Dma, suppressed the overproduction of PGE(2) and the expression of COX-2 and PGE synthase-1 induced by IL-13. In ovalbumin-induced asthma, Dma Suppressed AHR more strongly than Allo. These findings suggest that Dma attenuates asthmatic responses induced by IL-13 without affecting PGE(2) synthesis. Dma may have potential as therapeutic agents for asthma. (C) 2009 Elsevier Inc. All rights reserved.