Proteases and antiproteases in chronic neutrophilic lung disease – relevance to drug discovery

Proteases and antiproteases in chronic neutrophilic lung disease – relevance to drug discovery Chronic inflammatory lung diseases such as cystic fibrosis and emphysema are characterized by higher‐than‐normal levels of pulmonary proteases. While these enzymes play important roles such as bacterial killing, their dysregulated expression or activity can adversely impact on the inflammatory process. The existence of efficient endogenous control mechanisms that can dampen or halt this overexuberant protease activity in vivo is essential for the effective resolution of inflammatory lung disease. The function of pulmonary antiproteases is to fulfil this role. Interestingly, in addition to their antiprotease activity, protease inhibitors in the lung also often possess other intrinsic properties that contribute to microbial killing or termination of the inflammatory process. This review will outline important features of chronic inflammation that are regulated by pulmonary proteases and will describe the various mechanisms by which antiproteases attempt to counterbalance exaggerated protease‐mediated inflammatory events. These proteases, antiproteases and their modifiers represent interesting targets for therapeutic intervention. This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Proteases and antiproteases in chronic neutrophilic lung disease – relevance to drug discovery

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Publisher
Wiley
Copyright
© 2009 The Authors. Journal compilation © 2009 The British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
D.O.I.
10.1111/j.1476-5381.2009.00448.x
Publisher site
See Article on Publisher Site

Abstract

Chronic inflammatory lung diseases such as cystic fibrosis and emphysema are characterized by higher‐than‐normal levels of pulmonary proteases. While these enzymes play important roles such as bacterial killing, their dysregulated expression or activity can adversely impact on the inflammatory process. The existence of efficient endogenous control mechanisms that can dampen or halt this overexuberant protease activity in vivo is essential for the effective resolution of inflammatory lung disease. The function of pulmonary antiproteases is to fulfil this role. Interestingly, in addition to their antiprotease activity, protease inhibitors in the lung also often possess other intrinsic properties that contribute to microbial killing or termination of the inflammatory process. This review will outline important features of chronic inflammation that are regulated by pulmonary proteases and will describe the various mechanisms by which antiproteases attempt to counterbalance exaggerated protease‐mediated inflammatory events. These proteases, antiproteases and their modifiers represent interesting targets for therapeutic intervention. This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009

Journal

British Journal of PharmacologyWiley

Published: Oct 1, 2009

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