Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: Potential implications in asthma and other lung diseases

In healthy lung, Matrix Metalloproteinases (MMPs) and their physiological inhibitors, tissue inhibitors of matrix metalloproteinases (TIMPs), are produced in the respiratory tract by a panel of different structural cells. These activities are mandatory for many physiological processes including development, wound healing and cell trafficking. Deregulation of proteolytic-antiproteolytic network and inappropriate secretion of various MMPs by Stimulated Structural or inflammatory cells is thought to take pail to pathophysiology of numerous lung diseases including asthma, chronic obstructive pulmonary disease (COPD), lung fibrosis and lung cancer. Cytokines and growth factors are involved in these inflammatory processes and some of those mediators interact directly with MMPs and TIMPs leading either to a regulation of their expression or changes in their biological activities by proteolytic cleavage. In turn, cytokines and growth factors modulate secretion of MMPs establishing a complex network of reciprocal interactions. Every MMP seem to play a rather specific role and some variations of their expression are observed in different lung diseases. The precise role of these enzymes and their inhibitors is now studied in depth as they Could represent relevant therapeutic targets for many diseases. Indeed, MMP inhibition call lead either to a decrease of the intensity of a pathological process or, ill the contrary for some of them, to all increase of disease severity. In this review, we focus oil the role played by MMPs and TIMPs in asthma and we provide all overview of their potential roles in COPD, lung fibrosis and lung cancer, with a special emphasis oil loops including MMPs and cytokines and growth factors relevant in these diseases. (c) 2006 Elsevier B.V. All rights reserved.