Role of matrix metalloproteinases in asthma.
Airway inflammation and remodeling are key features of asthma. Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs) are thought to contribute to the pathogenesis of asthma via their influence on the function and migration of inflammatory cells as well as matrix deposition and degradation. TIMPs bind MMPs in a 1:1 fashion. Thus, an increase in the molar ratio of MMP/TIMP may favor tissue injury, while the reverse could be associated with increased fibrosis. MMP-9 is the predominant MMP in asthma, and its expression is enhanced when patients have spontaneous exacerbations or in response to local instillation of allergen in the airway. As acute inflammation resolves, MMP-9 levels return toward normal. Interestingly, corticosteroids downregulate MMP and enhance TIMPs. Even though it is clear that enhanced airway inflammation in asthma is associated with increased expression of MMPs, whether specific inhibitors of MMP could reduce airway injury and facilitate orderly healing in asthma is still unknown.
Kelly
Elizabeth A
EA
The Pulmonary and Critical Care Section of the Department of Medicine, University of Wisconsin, Madison, 53972, USA.
Jarjour
Nizar N
NN
D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D019714:Tissue Inhibitor of Metalloproteinases / Q000008:administration & dosage
D016326:Extracellular Matrix Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases