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首页> 外文期刊>Life sciences >Tryptase mediates hyperresponsiveness in isolated guinea pig bronchi.
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Tryptase mediates hyperresponsiveness in isolated guinea pig bronchi.

机译：类胰蛋白酶介导分离的豚鼠支气管高反应性。

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摘要

Hyperresponsiveness of airway smooth muscle to allergens and environmental factors has long been associated with the pathophysiology of asthma. Tryptase, a serine protease of lung mast cells, has been implicated as one of the mediators involved in the induction of hyperresponsiveness. As a consequence, tryptase inhibitors have become the subject of study as potential novel therapeutic agents for asthma. Secretory leukocyte protease inhibitor (SLPI) is a naturally occurring protein of human airways which exhibits anti-tryptase activity. To assess the potential therapeutic utility of SLPI in asthma, its effects were evaluated using in vitro and ex vivo models of airway hyperresponsiveness and compared with the effects of the small molecule tryptase inhibitor APC-366. Our results demonstrate that SLPI inhibits tryptase-mediated hyperresponsiveness in vitro and attenuates the hyperresponsiveness observed in airway smooth muscle from antigen-sensitized animals subjected to antigen exposure. The small molecule tryptase inhibitor APC-366 has a similar inhibitory effect. Thus, tryptase appears to be a significant contributor to the development of hyperresponsiveness in these models. To the extent that tryptase contributes to the development and progression of asthma, SLPI may possess therapeutic potential in this disease setting.
机译：长期以来，气道平滑肌对过敏原和环境因素的反应过度与哮喘的病理生理有关。类胰蛋白酶，一种肺肥大细胞的丝氨酸蛋白酶，被认为是诱导高反应性的一种介体。结果，类胰蛋白酶抑制剂已经作为潜在的新型哮喘治疗剂成为研究的主题。分泌型白细胞蛋白酶抑制剂（SLPI）是人呼吸道的天然蛋白质，具有抗胰蛋白酶活性。为了评估SLPI在哮喘中的潜在治疗作用，使用气道高反应性的体外和离体模型评估了其作用，并与小分子类胰蛋白酶抑制剂APC-366的作用进行了比较。我们的结果表明，SLPI在体外抑制类胰蛋白酶介导的反应过度，并减弱抗原暴露的抗原敏感动物在气道平滑肌中观察到的反应过度。小分子类胰蛋白酶抑制剂APC-366具有类似的抑制作用。因此，类胰蛋白酶似乎是这些模型中高反应性发展的重要因素。在一定程度上，类胰蛋白酶有助于哮喘的发生和发展，SLPI在这种疾病中可能具有治疗潜力。

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