The Serpin Superfamily and Their Role in the Regulation and Dysfunction of Serine Protease Activity in COPD and Other Chronic Lung Diseases

Abstract

Chronic obstructive pulmonary disease (COPD) is a debilitating heterogeneous disease characterised by unregulated proteolytic destruction of lung tissue mediated via a protease-antiprotease imbalance. In COPD, the relationship between the neutrophil serine protease, neutrophil elastase, and its endogenous inhibitor, alpha-1-antitrypsin (AAT) is the best characterised. AAT belongs to a superfamily of serine protease inhibitors known as serpins. Advances in screening technologies have, however, resulted in many members of the serpin superfamily being identified as having differential expression across a multitude of chronic lung diseases compared to healthy individuals. Serpins exhibit a unique suicide-substrate mechanism of inhibition during which they undergo a dramatic conformational change to a more stable form. A limitation is that this also renders them susceptible to disease-causing mutations. Identification of the extent of their physiological/pathological role in the airways would allow further expansion of knowledge regarding the complexity of protease regulation in the lung and may provide wider opportunity for their use as therapeutics to aid the management of COPD and other chronic airways diseases.

Data-Independent Acquisition and Quantification of Extracellular Matrix from Human Lung in Chronic Inflammation-Associated Carcinomas

“…SERPINB6 interacts with cathepsin G in monocytes and granulocytes to inhibit this inflammation-related protein and interacts with other trypsin-like proteases as well [74]. SERPINB5 has a tumor suppressive activity [74]. In LSCC, this protein may be associated with cancer development by regulating the p53 signaling pathway [75].…”

Current Insights on the Impact of Proteomics in Respiratory Allergies

“…Both APOH and SERPINB3 are upregulated in AR, suggesting that APOH may be involved in an upregulated state in rhinitis, while SERPINB3 acts at different stages of pathogenesis [ 36 ]. SERPINB3 is upregulated in asthma patients and mediates mucus production [ 37 ], also in chronic obstructive pulmonary disease (COPD) [ 38 ]. SERPINB3 is physiologically involved in the regulation of differentiation in the normal squamous epithelium and is overexpressed in neoplastic tissue of epithelial origin, where it might be involved in the apoptotic pathway as a protease inhibitor.…”

Enzymes in the time of COVID‐19: An overview about the effects in the human body, enzyme market, and perspectives for new drugs

“… 145 In addition, it is worthy to mention that exacerbated proteolytic activities contribute to respiratory diseases, for instance, asthma, cystic fibrosis, chronic obstructive pulmonary disease, acute lung injury and ARDS. 146 …”

“…This regulation occurs when, during inflammation, α 1 ‐antitrypsin present in tissues complexes with neutrophil elastase, this leads neutrophils, monocytes and alveolar macrophages to increase the expression of α 1 ‐antitrypsin and its plasma concentration is increased 145 . In addition, it is worthy to mention that exacerbated proteolytic activities contribute to respiratory diseases, for instance, asthma, cystic fibrosis, chronic obstructive pulmonary disease, acute lung injury and ARDS 146 …”

“…145 In addition, it is worthy to mention that exacerbated proteolytic activities contribute to respiratory diseases, for instance, asthma, cystic fibrosis, chronic obstructive pulmonary disease, acute lung injury and ARDS. 146 Moreover, SERPINs acting as a "trap" to target proteases 135 and inhibiting them 34 suggests that SERPINs may be used as treatment for pathologies caused by enzymes. 135 Besides, SERPINs play some roles in infections, for instance, by inhibiting pathogenproteases and pathogen binding, by preventing host apoptosis caused by pathogen invasion, and by enhancing host immune system.…”