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

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.

• Authors: T Cawston, S Carrere, J Catterall, R Duggleby, S Elliott, B Shingleton, A Rowan
• Journal: Novartis Foundation symposium (Novartis Found Symp) Vol. 234 Pg. 205-18; discussion 218-28 ( 2001) ISSN: 1528-2511 [Print] England
• PMID: 11199097 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Tissue Inhibitor of Metalloproteinases
• Matrix Metalloproteinases

Topics

• Animals
• Humans
• Lung Diseases (enzymology)
• Lung Diseases, Obstructive (drug therapy, enzymology)
• Matrix Metalloproteinases (immunology, metabolism, therapeutic use)
• Tissue Inhibitor of Metalloproteinases (immunology, metabolism)