Simultaneous up-regulation of matrix metalloproteinases 1, 2, 3, 7, 8, 9 and tissue inhibitors of metalloproteinases 1, 4 in serum of patients with chronic obstructive pulmonary disease.

ABSTRACT

BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. However, the majority of studies have focused on single MMP, and there is limited information on parallel expression of MMP and their antagonists TIMP. We, therefore, investigated the serum profile of MMP 1-3, 7-9, 12 and 13, and TIMP 1-4 in COPD patients. METHODS: Serum MMP 1-3, 7-9, 12 and 13, and TIMP 1-4 were measured in 74 COPD patients and 20 control subjects by multiple microsphere technology. RESULTS: MMP 1-3 and MMP 7-9 were elevated in COPD patients compared with control subjects (P= 0.001-0.043). The increased concentrations of MMP 1, 8 and 9 paralleled GOLD stage (P= 0.002-0.007). TIMP 1 and 4 concentrations were elevated in COPD (P < 0.001). MMP 1, 8 and 9, and TIMP 1 and 4 serum levels in COPD non-smokers were higher than in control non-smokers (P = 0.002-0.025). MMP 12 and 13 levels were undetectable in our serum samples. CONCLUSIONS: This study provides further evidence for increased MMP 1, 7-9, and TIMP 1 serum levels in COPD, and demonstrates for the first time serum elevation of MMP 2 and 3, and TIMP 4. The finding that circulating TIMP 4 levels are increased in COPD and the observed relationship between serum levels of MMP 1, 8 and 9, and GOLD stage requires verification in an expanded patient cohort.