Induced sputum metalloproteinases and their inhibitors in relation to exhaled nitrogen oxide and sputum nitric oxides and other inflammatory cytokines in patients with chronic obstructive pulmonary disease

J Physiol Pharmacol. 2008 Dec:59 Suppl 6:809-17.

Abstract

The aim of this study was to assess sputum levels of the metalloproteinases MMP-1, MMP-2, MMP-3, TIMP-1, and TIMP-2, as well as MMPs/TIMPs ratios in relation to exhaled NO (eNO) and sputum NOs (nitrates and nitrites) and IL8 obtained from chronic obstructive pulmonery disease (COPD) patients, healthy non-smokers, and healthy smokers. We found higher levels of TIMP-1 (118.9 ng/ml) and TIMP-2 (3.75 ng/ml) in COPD patients than in healthy smokers (17.7 ng/ml, P<0.03; 0.51 ng/ml, P>0.05, respectively) and healthy non-smokers (84.6 ng/ml, P>0.05; 1.61 ng/ml, P>0.05, respectively). We also observed significant positive correlations between concentrations of NOs and MMP-1, MMP-2, MMP-3, and TIMP-2 (r=0.37, P<0.02; r=0.60, P<0.0001; r=0.56, P<0.0004 and r=0.47 P<0.004, respectively) in COPD patients. IL8, MMP-2, MMP-3, and TIMP-2 levels in induced sputum were negatively correlated with airway obstruction, i.e., FEV(1)/FVC (r=-0.61, P<0.00009; r=-0.41, P<0.01; r=-0.38, P<0.02; r=-0.49, P<0.002). Our study points to a potentially pathogenic role of stromelysin-1 (MMP-3) in COPD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytokines / biosynthesis*
  • Extracellular Space / enzymology
  • Extracellular Space / metabolism
  • Female
  • Humans
  • Leukocyte Count
  • Male
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinase 3 / physiology
  • Matrix Metalloproteinases / metabolism*
  • Middle Aged
  • Nitric Oxide / metabolism*
  • Nitrogen Oxides / metabolism*
  • Protease Inhibitors / metabolism*
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Respiratory Function Tests
  • Smoking / metabolism
  • Spirometry
  • Sputum / enzymology*

Substances

  • Cytokines
  • Nitrogen Oxides
  • Protease Inhibitors
  • Nitric Oxide
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 3