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蛋白酶 3;慢性阻塞性肺疾病和其他慢性炎症性疾病的潜在靶点。

Proteinase 3; a potential target in chronic obstructive pulmonary disease and other chronic inflammatory diseases.

机构信息

Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, B15 2GW, UK.

Institute of Inflammation and Ageing, College of Medical and Dental Sciences, Centre for Translational Inflammation Research, University of Birmingham Research Laboratories, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2WB, UK.

出版信息

Respir Res. 2018 Sep 20;19(1):180. doi: 10.1186/s12931-018-0883-z.

Abstract

Chronic Obstructive Pulmonary Disease (COPD) is a common, multifactorial lung disease which results in significant impairment of patients' health and a large impact on society and health care burden. It is believed to be the result of prolonged, destructive neutrophilic inflammation which results in progressive damage to lung structures. During this process, large quantities of neutrophil serine proteinases (NSPs) are released which initiate the damage and contribute towards driving a persistent inflammatory state.Neutrophil elastase has long been considered the key NSP involved in the pathophysiology of COPD. However, in recent years, a significant role for Proteinase 3 (PR3) in disease development has emerged, both in COPD and other chronic inflammatory conditions. Therefore, there is a need to investigate the importance of PR3 in disease development and hence its potential as a therapeutic target. Research into PR3 has largely been confined to its role as an autoantigen, but PR3 is involved in triggering inflammatory pathways, disrupting cellular signalling, degrading key structural proteins, and pathogen response.This review summarises what is presently known about PR3, explores its involvement particularly in the development of COPD, and indicates areas requiring further investigation.

摘要

慢性阻塞性肺疾病(COPD)是一种常见的、多因素的肺部疾病,导致患者的健康受到严重损害,对社会和医疗保健负担产生重大影响。据信,它是由于长期、破坏性的中性粒细胞炎症导致肺结构进行性损伤的结果。在此过程中,大量中性粒细胞丝氨酸蛋白酶(NSP)被释放,引发损伤并促使持续的炎症状态。中性粒细胞弹性蛋白酶长期以来一直被认为是参与 COPD 病理生理学的关键 NSP。然而,近年来,蛋白酶 3(PR3)在 COPD 和其他慢性炎症性疾病的发病机制中的作用已经凸显出来。因此,有必要研究 PR3 在疾病发展中的重要性,从而探讨其作为治疗靶点的潜力。PR3 的研究主要局限于其作为自身抗原的作用,但 PR3 参与触发炎症途径、破坏细胞信号、降解关键结构蛋白和病原体反应。本综述总结了目前对 PR3 的了解,探讨了其在 COPD 发展中的特殊作用,并指出了需要进一步研究的领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e13f/6149181/41fe01495467/12931_2018_883_Fig1_HTML.jpg

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