Enhanced levels of prostaglandin E2 and matrix metalloproteinase-2 correlate with the severity of airflow limitation in stable COPD.
OBJECTIVE
Cyclooxygenase-2 (COX-2) and its product prostaglandin E2 (PGE2) 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 PGE2 and MMP-2, and to investigate the role of COX-2 and PGE2 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 nonsmoking control subjects were enrolled. Induced sputum was obtained for measurement of the concentrations of PGE2 and MMP-2 by ELISA. COX-2 protein expression was assessed by western blotting.


RESULTS
PGE2 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 PGE2 andMMP-2 were inversely correlated with FEV1%predicted in COPD patients (PGE2: r = -0.748, P < 0.01; MMP-2: r = -0.801, P < 0.01). Levels of PGE2 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 PGE2 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.
Chen
Yan
Y
Department of Internal Medicine, Division of Respiratory Disease, The Second Xiangya Hospital,Central-South University, Changsha, Hunan, China.
Chen
Ping
P
Hanaoka
Masayuki
M
Droma
Yunden
Y
Kubo
Keishi
K
D000403:Airway Resistance / Q000502:physiology*; D001249:Asthma / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D008875:Middle Aged; D012720:Severity of Illness Index; D013183:Sputum / Q000737:chemistry*; D013997:Time Factors
D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2; D015232:Dinoprostone