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Matrix metalloproteinases and TIMPs: Properties and implications for the treatment of chronic obstructive pulmonary disease

Lookup NU author(s): Emeritus Professor Tim Cawston, Dr Severine Carrere, Dr Jonathan Catterall, Dr Richard Duggleby, Suzanne Elliott, Emeritus Professor Drew Rowan

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Abstract

The matrix metalloproteinases (MMPs) are a unique family of metalloenzymes that, once activated, can destroy connective tissue. The active enzymes are all inhibited by tissue inhibitors of metalloproteinases (TIMPs). The relative amounts of active MMPs and TIMPs are important in determining whether tissues are broken down in disease. Although elastase is often regarded as the target enzyme in chronic obstructive pulmonary disease (COPD), both the neutrophils and macrophages in the lung contain metalloproteinases and both collagen and elastin are degraded in disease. Transgenic studies have shown that when MMP1 is over-expressed, pulmonary emphysema develops in mice, while MMP12 knockout mice do not develop pulmonary emphysema when exposed to cigarette smoke. New drugs that can specifically block active MMPs are now available. These potent inhibitors are effective in vitro and prevent the destruction of tissue in animal models. Future patient trials will test the effectiveness of these compounds in preventing tissue destruction.


Publication metadata

Author(s): Cawston TE, Carrere SL, Catterall JB, Duggleby RC, Elliott SC, Shingleton B, Rowan AD

Editor(s): Chadwick D, Goode JA

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: Novartis Foundation Symposium 234: Chronic Obstructive Pulmonary Disease: Pathogenesis to Treatment

Year of Conference: 2001

Pages: 205-228

ISSN: 9780471494379

Publisher: Chichester: Wiley

URL: http://dx.doi.org/10.1002/0470868678.ch13

DOI: 10.1002/0470868678.ch13

PubMed id: 11199097

Library holdings: Search Newcastle University Library for this item

Series Editor(s): Novartis Foundation

ISBN: 9780470868676


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