Abstract
There is considerable evidence that matrix metalloproteinases (MMPs) are up- and/or downregulated in chronic obstructive pulmonary disease (COPD), particularly in emphysema, in which they probably participate in proteolytic attack on the alveolar wall matrix. Recent data suggest that MMPs also have major roles in driving inflammation or shutting it down, as well as modifying the release of fibrogenic growth factors, processes that are important in the genesis of the various lesions of COPD. In cigarette smoke-induced animal models of emphysema, MMP-12 appears to play a consistent and important role, whereas the data for other MMPs are difficult to interpret. In human lungs, evidence for a role for MMPs is more tenuous and there are numerous contradictions in the literature. Little is known about the effects of MMPs in small airway remodelling, smoke-induced pulmonary hypertension and chronic bronchitis, but MMP-12 participates in experimental small airway modelling. To date, the accumulated data suggest that selective inhibition of MMP-12 might be a viable therapy for emphysema and small airway remodelling, but subtle differences in the functions of MMP-12 in animals and humans mandate caution with this approach. Whether inhibition of other MMPs might be useful is unclear.
- Cigarette smoke
- chronic obstructive pulmonary disease
- emphysema
- matrix metalloproteinases
- matrix metalloproteinase-12
- small airway remodelling
Footnotes
Previous articles in this Series: No. 1: Löffek S, Schilling O, Franzke C-W. Biological role of matrix metalloproteinases: a critical balance. Eur Respir J 2011; 38: 191–208. No. 2: Elkington PT, Ugarte-Gil CA, Friedland JS. Matrix metalloproteinases in tuberculosis. Eur Respir J 2011; 38: 456–464. No. 3: Gaggar A, Hector A, Bratcher PE, et al. The role of matrix metalloproteinases in cystic fibrosis lung disease. Eur Respir J 2011; 38: 721–727. No. 4: Davey A, McAuley DF, O’Kane CM. Matrix metalloproteinases in acute lung injury: mediators of injury and drivers of repair. Eur Respir J 2011; 38: 959–970. No. 5: Vandenbroucke RE, Dejonckheere R, Libert C. A therapeutic role for matrix metalloproteinase inhibitors in lung diseases? Eur Respir J 2011; 38: 1200–1214. No. 6: Dancer RCA, Wood AM, Thickett DR. Metalloproteinases in idiopathic pulmonary fibrosis. Eur Respir J 2011; 38: 1461–1467.
Statement of Interest
Statements of interest for A. Churg and J.L. Wright can be found at www.erj.ersjournals.com/site/misc/statements.xhtml
- Received July 15, 2011.
- Accepted August 27, 2011.
- ©ERS 2012