Anti-inflammatory properties of MMP inhibitors in experimental models of chronic obstructive pulmonary disease and lung inflammation
Matrix metalloproteinases (MMPs) are a group of proteases known to regulate the turnover of extracellular matrix and thus are suggested to be important in the process of lung disease associated with tissue remodelling. Furthermore, the concept that modulation of airway remodelling including excessive proteolysis damage of the tissue, may be of interest as a basis for future treatment. Among the metalloproteinases (MMPs) family, macrophage elastase (MMP-12) is able to degrade extracellular matrix components such as elastin and is involved in tissue remodelling processes in chronic obstructive pulmonary disease including emphysema. Recent studies using broad spectrum MMP or dual MMP-9/MMP-12 inhibitors have demonstrated a reduction in both inflammatory process and airspace enlargement in lung tissue. In the present chapter, we also report the inhibitory activity of a new MMP-9/MMP-12 inhibitor, AS112108, on acute lung inflammatory processes induced by cigarette smoke.
KeywordsChronic Obstructive Pulmonary Disease Cigarette Smoke Chronic Obstructive Pulmonary Disease Patient Respir Crit Cigarette Smoke Exposure
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- 12.Kang MJ, Oh YM, Lee JC, Kim DG, Park MJ, Lee MG, Hyun IG, Han SK, Shim YS, Jung KS (2003) Lung matrix metalloproteinase-9 correlates with cigarette smoking and obstruction of airflow. J Kor Med Sci 18: 821–827Google Scholar
- 14.Russell RE, Culpitt SV, DeMatos C, Donnelly L, Smith M, Wiggins J, Barnes PJ (2002) Release and activity of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 26: 602–609PubMedGoogle Scholar
- 15.Russell RE, Thorley A, Culpitt SV, Dodd S, Donnelly LE, Demattos C, Fitzgerald M, Barnes PJ (2002) Alveolar macrophage-mediated elastolysis: roles of matrix metalloproteinases, cysteine, and serine proteases. Am J Physiol Long Cell Mol Physiol 283: L867–L873Google Scholar