Relationship Between Matrix Metalloproteinase And Chronic Obstructive Pulmonary Disease

ObjectiveIn order to investigate the relationship of the changes of MMP-9/TIMP-1 with airflow obstruction and airway inflammation in patients with COPD by detecting the levels of MMP-9, TIMP-1, IL-8, IL-17, TGF-β1 and inflammatory cell in sputum and serum.MethodsSputum supernatant samples from 26 patients with COPD, and 16 health subjects were collected and analyzed. Sputum induction was performed by inhalation of hypertonic saline solution after premedication with inhaled salbutamol 400μg. Sputum cells were counted after cytospin preparation and stained with Right's staining to assess the quality of the samples. The concentrations of MMP-9,TIMP-1,IL-8,IL-17 and TGF-β1 in sputum supernatant and serum were measured using enzyme-linked immunosorbent assay.Results1. The total counts of cells, neutrophils and the percentage of neutrophils in sputum samples from exacerbation group of COPD were higher than that in the stable (P＜0.01) and the control (P＜0.01). There were significant differences between the stable and the control (P＜0.01). The counts of lymphocyte, Macrophage and eosinophil in sputum during the acute exacerbation and the stable were higher than that of the control (P＜0.01). but There was no difference of the counts of lymphocyte, Macrophage and eosinophil in sputum between the stable and the control(p＞0.05).2.The levels of MMP-9 and TIMP-1 in sputum samples from exacerbation group of COPD were higher than that in stable group of COPD (p＜0.01) and control group (p＜0.01), and the levels of MMP-9 and TIMP-1 in stable group were higher than that in control group (p＜0.01); The ratio of MMP-9/TIMP-1 in exacerbation group of COPD was higher than that in stable group of COPD (p＜0.01) and control group (p＜0.01), and the ratio of MMP-9/TIMP-1 in stable group was higher than that in control group(p＜0.01); The sputum levels of IL-8, IL-17 and TGF-β1 in exacerbation group of COPD were higher than that in stable group (p＜0.01) and control group(p＜0.01); There was no significant difference of sputum levels of IL-8, IL-17, TGF-β1 between stable group and control group (p＞0.05).3.The counts of neutrophil, lymphocyte, macrophage, eosinophil in sputum were shown to be positively correlated with sputum levels of MMP-9 in exacerbation group(p＜0.01), There were significantly positive correlation between the ratio of MMP-9/TIMP-1 and the counts of neutrophil, lymphocyte, macrophage, eosinophil in sputum in exacerbation group(p＜0.01), but the level of TIMP-1 was no correlation with the counts of neutrophil, lymphocyte, macrophage, eosinophil (p＞0.05). There were no significant correlation between the levels of MMP-9 and the counts of neutrophil, lymphocyte, macrophage, eosinophil in sputum in stable group(p＞0.05), the level of TIMP-1 was positive correlation with the counts ofmacrophage(Rho=0.487, p=0.012) and no correlation with the counts of neutrophil, lymphocyte, eosinophil in sputum in stable group(p＞0.05), There were no significant correlation between the ratio of MMP-9/TIMP-1 and the counts of neutrophil, lymphocyte, macrophage, eosinophil in sputum in stable group(p＞0.05).4. The levels of IL-8, IL- 17 and TGF-β1 were shown to be positively correlated with both the sputum levels of MMP-9 (Rho=0.878, 0.835, 0.847, p＜0.05) and TIMP-1 (Rho=0.446, 0.458, 0.535, p＜0.05) in exacerbation group; The ratio of MMP-9/TIMP-1 was positively correlated with IL-8, IL-17 and TGF-β1 in exacerbation group (Rh0=0.653, 0.595, 0.545, p＜0.01)The sputum levels of MMP-9 and TIMP-1 were positively correlated with IL-8 and TGF-β1 in stable group (Rh0=0.442, 0.396, p＜0.05; Rh0=0.489, 0.504, p＜0.05); There were no correlation between the sputum levels of MMP-9 and sputum IL-17(Rh0=0.340, p=0.089) in stable group; There were positive correlation between the sputum levels ofTIMP-1 and sputum IL-17(Rh0=0.488, p＜0.05) in stable group; There were no correlation between the ratio of sputum MMP-9/TIMP-1 and sputum levels of IL-8,IL-17 and TGF-β1 IL-17(p＞0.05) in stable group.5. The sputum levels of MMP-9 and TIMP-1 and the ratio of sputum MMP-9/TIMP-1 were shown no correlation with FEV1/Pred% and FEV1/FVC in exacerbation group. The sputum levels of MMP-9 and TIMP-1 were shown to be negatively correlated with FEV1/Pred% and FEV1/FVC (Rh0=-0.568,-0.542,p＜0.01; Rh0=-0.677,-0.622, p＜0.01) in stable group; There were no correlation between the ratio of sputum MMP-9/TIMP-1 and FEVI/Pred%, FEV1/FVC (Rh0=-0.187,-0.182,p＞0.05) in stable group.6. The serum levels of MMP-9 and TIMP-1 in exacerbation group of COPD were higher than that in stable group of COPD (p＜0.01) and control group (p＜0.01); There were no significant difference of the serum levels of MMP-9 between the stable group and the control group(p＞0.05); The serum levels of TIMP-1 in stable group were higher than that in control group(p＜0.01); The ratio of serum MMP-9/TIMP-1 in exacerbation group of COPD were higher than that in stable group of COPD (p＜0.01) and control group(p＜0.01); There were no significant difference of the ratio of serum MMP-9/TIMP-1 between the stable group and control group(p＞0.05).7. The levels of MMP-9 and TIMP-1 in serum samples from exacerbation group of COPD were positive correlations with the counts of neutrophil, lymphocyte, macrophage, eosinophil in sputum, the ratio of MMP-9/TIMP-1 in serum were positive correlations with the counts of neutrophil(Rho=0.585, p=0.002), but there was no correlation between the ratio of MMP-9/TIMP-1 and the counts of lymphocyte, macrophage, eosinophil in exacerbation group; The levels of MMP-9 and TIMP-1 and the ratio of MMP-9/TIMP-1 in serum in stable group of COPD were no correlations with the counts of neutrophil, lymphocyte, macrophage, eosinophil in sputum.8. The serum levels of IL-8, IL-17 and TGF-β1 were shown to be positively correlated with both the serum levels of MMP-9(Rho=0.717, 0.847, 0.687, p＜0.01) and TIMP-1 (Rho=0.454, 0.590, 0.801, p＜0.05) in exacerbation group; The ratio of MMP-9/TIMP-1 was positively correlated with IL-8, IL-17 in exacerbation group (Rh0=0.408,0.414, p＜0.05) and was no correlation with TGF-β1(Rh0=0.213, p＞0.05); There were no correlation between MMP-9 and the ratio of MMP-9/TIMP-1 and serum levels ofIL-8,IL-17 and TGF-β1(p＞0.05) in stable group, There were positive correlation between the serum levels of TIMP-1 and IL-8 and TGF-β1 (Rh0=0.441,0.449,p＜0.05) in stable group, There were no correlation between the serum levels of TIMP-1 and IL-17 in stable group.9. The serum levels of MMP-9 and TIMP-1 and the ratio of MMP-9/TIMP-1 were shown no correlation with FEV1/Pred% and FEV1/FVC in exacerbation group, The serum levels of MMP-9 were shown to be negatively correlated with FEV1/Pred% (Rh0=-0.418, p＜0.05) in stable group; The serum levels of TIMP-1 were shown to be negatively correlated with FEV1/Pred% and FEV1/FVC (Rh0=-0.482, -0.446, p＜0.05) in stable group; the ratio of MMP-9/TIMP-1 were shown no correlation with FEV 1/Pred% and FEV1/FVC in stable group.10. The levels of MMP-9 in sputum were shown to be positively correlated with that in serum in exacerbation group (Rh0=0.861, p＜0.01); There were no correlation between the levels of TIMP-1 in sputum and that in serum in exacerbation group; There were no correlation between the ration of MMP-9/TIMP-1 in sputum and that in serum in exacerbation group.The levels of MMP-9 in sputum were shown to be positively correlated with that in serum in stable group (Rh0=0.518, p＜0.01 ); The levels of TIMP-1 in sputum were showed to be positively correlated with thai in serum in stable group (Rh0=0.560, p＜0.01); There were no correlation between the ration of MMP-9/TIMP-1 in sputum and that in serum in stable group.ConclusionMMP-9 and TIMP-1 play important roles in the airway inflammation of COPD during the exacerbation and stable stage, the imbalance of MMP-9/TIMP-1 takes part in airway inflammation and airflow obstruction. COPD is probably a systemic inflammatory disease.