Protease-antiprotease imbalance in bronchiectasis

Airway inflammation plays a central role in bronchiectasis. Protease-antiprotease balance is crucial in bronchiectasis pathophysiology and increased presence of unopposed proteases activity may contribute to bronchiectasis onset and progression. Proteases' over-reactivity and antiprotease defic...

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Main Authors: Oriano, Martina, Amati, Francesco, Gramegna, Andrea, De Soyza, Anthony, Mantero, Marco, Sibila, Oriol, Chotirmall, Sanjay Haresh, Voza, Antonio, Marchisio, Paola, Blasi, Francesco, Aliberti, Stefano
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2021
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Online Access:https://hdl.handle.net/10356/152081
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1520812023-03-05T16:44:15Z Protease-antiprotease imbalance in bronchiectasis Oriano, Martina Amati, Francesco Gramegna, Andrea De Soyza, Anthony Mantero, Marco Sibila, Oriol Chotirmall, Sanjay Haresh Voza, Antonio Marchisio, Paola Blasi, Francesco Aliberti, Stefano Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Bronchiectasis Proteases Airway inflammation plays a central role in bronchiectasis. Protease-antiprotease balance is crucial in bronchiectasis pathophysiology and increased presence of unopposed proteases activity may contribute to bronchiectasis onset and progression. Proteases' over-reactivity and antiprotease deficiency may have a role in increasing inflammation in bronchiectasis airways and may lead to extracellular matrix degradation and tissue damage. Imbalances in serine proteases and matrix-metallo proteinases (MMPs) have been associated to bronchiectasis. Active neutrophil elastase has been associated with disease severity and poor long-term outcomes in this disease. Moreover, high levels of MMPs have been associated with radiological and disease severity. Finally, severe deficiency of α1-antitrypsin (AAT), as PiSZ and PiZZ (proteinase inhibitor SZ and ZZ) phenotype, have been associated with bronchiectasis development. Several treatments are under study to reduce protease activity in lungs. Molecules to inhibit neutrophil elastase activity have been developed in both oral or inhaled form, along with compounds inhibiting dipeptydil-peptidase 1, enzyme responsible for the activation of serine proteases. Finally, supplementation with AAT is in use for patients with severe deficiency. The identification of different targets of therapy within the protease-antiprotease balance contributes to a precision medicine approach in bronchiectasis and eventually interrupts and disrupts the vicious vortex which characterizes the disease. Published version 2021-11-18T07:14:30Z 2021-11-18T07:14:30Z 2021 Journal Article Oriano, M., Amati, F., Gramegna, A., De Soyza, A., Mantero, M., Sibila, O., Chotirmall, S. H., Voza, A., Marchisio, P., Blasi, F. & Aliberti, S. (2021). Protease-antiprotease imbalance in bronchiectasis. International Journal of Molecular Sciences, 22(11), 5996-. https://dx.doi.org/10.3390/ijms22115996 1661-6596 https://hdl.handle.net/10356/152081 10.3390/ijms22115996 34206113 2-s2.0-85106957968 11 22 5996 en International Journal of Molecular Sciences © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Bronchiectasis
Proteases
spellingShingle Science::Medicine
Bronchiectasis
Proteases
Oriano, Martina
Amati, Francesco
Gramegna, Andrea
De Soyza, Anthony
Mantero, Marco
Sibila, Oriol
Chotirmall, Sanjay Haresh
Voza, Antonio
Marchisio, Paola
Blasi, Francesco
Aliberti, Stefano
Protease-antiprotease imbalance in bronchiectasis
description Airway inflammation plays a central role in bronchiectasis. Protease-antiprotease balance is crucial in bronchiectasis pathophysiology and increased presence of unopposed proteases activity may contribute to bronchiectasis onset and progression. Proteases' over-reactivity and antiprotease deficiency may have a role in increasing inflammation in bronchiectasis airways and may lead to extracellular matrix degradation and tissue damage. Imbalances in serine proteases and matrix-metallo proteinases (MMPs) have been associated to bronchiectasis. Active neutrophil elastase has been associated with disease severity and poor long-term outcomes in this disease. Moreover, high levels of MMPs have been associated with radiological and disease severity. Finally, severe deficiency of α1-antitrypsin (AAT), as PiSZ and PiZZ (proteinase inhibitor SZ and ZZ) phenotype, have been associated with bronchiectasis development. Several treatments are under study to reduce protease activity in lungs. Molecules to inhibit neutrophil elastase activity have been developed in both oral or inhaled form, along with compounds inhibiting dipeptydil-peptidase 1, enzyme responsible for the activation of serine proteases. Finally, supplementation with AAT is in use for patients with severe deficiency. The identification of different targets of therapy within the protease-antiprotease balance contributes to a precision medicine approach in bronchiectasis and eventually interrupts and disrupts the vicious vortex which characterizes the disease.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Oriano, Martina
Amati, Francesco
Gramegna, Andrea
De Soyza, Anthony
Mantero, Marco
Sibila, Oriol
Chotirmall, Sanjay Haresh
Voza, Antonio
Marchisio, Paola
Blasi, Francesco
Aliberti, Stefano
format Article
author Oriano, Martina
Amati, Francesco
Gramegna, Andrea
De Soyza, Anthony
Mantero, Marco
Sibila, Oriol
Chotirmall, Sanjay Haresh
Voza, Antonio
Marchisio, Paola
Blasi, Francesco
Aliberti, Stefano
author_sort Oriano, Martina
title Protease-antiprotease imbalance in bronchiectasis
title_short Protease-antiprotease imbalance in bronchiectasis
title_full Protease-antiprotease imbalance in bronchiectasis
title_fullStr Protease-antiprotease imbalance in bronchiectasis
title_full_unstemmed Protease-antiprotease imbalance in bronchiectasis
title_sort protease-antiprotease imbalance in bronchiectasis
publishDate 2021
url https://hdl.handle.net/10356/152081
_version_ 1759853970574016512