Proteases, Mucus, and Mucosal Immunity in Chronic Lung Disease.
Proteases, Mucus, and Mucosal Immunity in Chronic Lung Disease.
复制标题
慢性肺疾病中的蛋白酶、粘液和粘液免疫。
DOI：
10.3390/ijms22095018
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发表时间：
2021-05-09
影响因子：
5.6
通讯作者：
Taggart CC
中科院分区：
文献类型：
--
作者：
McKelvey MC;Brown R;Ryan S;Mall MA;Weldon S;Taggart CC
长期以来，蛋白酶活性失调与慢性肺部疾病的发病机制有关，特别是在表现为粘液阻塞的情况下，如慢性阻塞性肺疾病、囊性纤维化和非囊性纤维化支气管扩张。然而，我们对蛋白酶在这些疾病的各个方面的作用的认识在不断增加。黏液阻塞性肺疾病患者经历炎症、粘膜停滞、气道感染和肺功能下降的进行性螺旋。已有一些治疗这些症状的疗法，但它们无法阻止疾病进展，患者可能受益于新的辅助疗法。在这篇综述中，我们强调了蛋白酶是如何作为对正常气道稳态至关重要的多功能酶，但当它们的活性变得不适度时，也会直接导致气道功能障碍，并损害可能解决疾病的过程。我们关注的是蛋白酶如何调节气道表面的粘液状态，损害粘膜纤毛清除，并最终促进粘膜稳定。同时，我们讨论了蛋白酶如何通过介导促炎信号、损害宿主防御机制和维持自身的蛋白水解活性来促进气道中的炎症环境，从而导致结构性肺损伤。最后，我们讨论了迄今为止蛋白酶抑制剂临床无效的一些可能原因，并提出，特别是在联合治疗方法中，蛋白酶是治疗黏液阻塞性肺疾病的有吸引力的治疗靶点。
Dysregulated protease activity has long been implicated in the pathogenesis of chronic lung diseases and especially in conditions that display mucus obstruction, such as chronic obstructive pulmonary disease, cystic fibrosis, and non-cystic fibrosis bronchiectasis. However, our appreciation of the roles of proteases in various aspects of such diseases continues to grow. Patients with muco-obstructive lung disease experience progressive spirals of inflammation, mucostasis, airway infection and lung function decline. Some therapies exist for the treatment of these symptoms, but they are unable to halt disease progression and patients may benefit from novel adjunct therapies. In this review, we highlight how proteases act as multifunctional enzymes that are vital for normal airway homeostasis but, when their activity becomes immoderate, also directly contribute to airway dysfunction, and impair the processes that could resolve disease. We focus on how proteases regulate the state of mucus at the airway surface, impair mucociliary clearance and ultimately, promote mucostasis. We discuss how, in parallel, proteases are able to promote an inflammatory environment in the airways by mediating proinflammatory signalling, compromising host defence mechanisms and perpetuating their own proteolytic activity causing structural lung damage. Finally, we discuss some possible reasons for the clinical inefficacy of protease inhibitors to date and propose that, especially in a combination therapy approach, proteases represent attractive therapeutic targets for muco-obstructive lung diseases.
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影响因子：
4.1
作者：
Averna, Monica;Stifanese, Roberto;Melloni, Edon
通讯作者：
Melloni, Edon
影响因子：
5.2
作者：
Barth, P.;Bruijnzeel, P.;Chevalier, E.
通讯作者：
Chevalier, E.
影响因子：
6.4
作者：
Berenson, Charles S.;Kruzel, Ragina L.;Sethi, Sanjay
通讯作者：
Sethi, Sanjay
影响因子：
4.4
作者：
Asokananthan, N;Graham, PT;Stewart, GA
通讯作者：
Stewart, GA
DOI：
10.1152/ajprenal.00179.2012
发表时间：
2013-09-01
影响因子：
4.2
作者：
Bao, Jialing;Yura, Renee E.;Bond, Judith S.
通讯作者：
Bond, Judith S.