Metalloproteinases as modulators of allergic asthma: therapeutic perspectives

Abstract

Matrix metalloproteinases (MMPs) are proteolytic enzymes that facilitate extracellular matrix turnover; thus, these enzymes are important in both normal wound repair and pathologic processes, such as inflammation and fibrosis. In addition, MMPs regulate cell signaling through proteolytic shedding of bioactive growth factors, cytokines, and other molecules. Therefore, the expression and activation of MMPs and their endogenous inhibitors, tissue inhibitors of metalloproteinases, play roles in the development of a variety of diseases. Allergic asthma is a chronic inflammatory disease of the airways that affects millions of patients, both children and adults, worldwide. Allergen-induced airway injury and immune responses stimulate airway inflammation, hyperresponsiveness, and remodeling in these patients. The action of MMPs links these pathologic processes through a complex interaction of airway inflammatory cells and structural cells. This review explores the important roles of MMPs and tissue inhibitors of metalloproteinases in mediating the pathobiology of allergic asthma and highlights the potential for these enzymes to serve as biomarkers or therapeutic targets in allergic asthma.