Enhanced levels of prostaglandin E2 and matrix metalloproteinase-2 correlate with the severity of airflow limitation in stable COPD

Background and objective: Cyclooxygenase-2 (COX-2) and its product prostaglandin E-2 (PGE(2)) have been demonstrated to play critical roles in inflammation in respiratory diseases. However, the role of COX-2 in airway remodelling in COPD remains to be elucidated. Matrix metalloproteinase-2 (MMP-2) is associated with both inflammation and airway remodelling in COPD. The objective of this study was to measure the expression of COX-2 and the concentrations of PGE(2) and MMP-2, and to investigate the role of COX-2 and PGE(2) in airflow limitation mediated by MMP-2, in the pathogenesis of COPD. Methods: Forty-three patients with stable COPD, twelve smoking control subjects and ten non-smoking control subjects were enrolled. Induced sputum was obtained for measurement of the concentrations of PGE(2) and MMP-2 by ELISA. COX-2 protein expression was assessed by western blotting. Results: PGE(2) and MMP-2 concentrations were significantly higher in both smoking control subjects and patients with COPD than in non-smoking control subjects (P < 0.01). Moreover, the levels of PGE(2) and MMP-2 were inversely correlated with FEV1% predicted in COPD patients (PGE(2): r = -0.748, P < 0.01; MMP-2: r = -0.801, P < 0.01). Levels of PGE(2) were also positively correlated with those of MMP-2 in patients with COPD (r = 0.775, P < 0.01). Expression of COX-2 protein was significantly higher in COPD patients than in non-smoking control subjects. Conclusions: COX-2 and its product PGE(2) are not only involved in airway inflammation, but may also contribute to the severity of airflow limitation mediated by MMP-2 during progression of COPD.