Expressions of MMP-12, TIMP-4, and Neutrophil Elastase in PBMCs and Exhaled Breath Condensate in Patients with COPD and Their Relationships with Disease Severity and Acute Exacerbations.

Wendong Hao,Cailian Zhang,Yunqing Zhang,Manxiang Li,Yani Xue

doi:10.1155/2019/7142438

Abstract

Objective The purpose of this study was to compare matrix metalloproteinase-12 (MMP-12), neutrophil elastase (NE), and tissue inhibitor of metalloproteinase-4 (TIMP-4) in peripheral blood of patients with chronic obstructive pulmonary disease (COPD) and controls. At the same time, MMP-12, NE, and TIMP-4 in exhaled breath condensate (EBC) were also evaluated. Methods Peripheral blood and EBC samples from COPD patients and healthy controls were collected. In serum and EBC, MMP-12, NE, and TIMP-4 proteins were detected by enzyme-linked immunoassays. The mRNA expression levels of MMP-12, NE, and TIMP-4 in peripheral blood mononuclear cells (PBMCs) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Results The concentration of TIMP-4 protein in EBC was lower in patients with COPD (P < 0.001). MMP-12 (P = 0.046), NE (P = 0.027), and TIMP-4 (P = 0.005) proteins in serum of patients with COPD showed higher levels of concentration. The mRNA of MMP-12 (P = 0.0067), NE (P = 0.0058), and TIMP-4 (P = 0.0006) in PBMCs of COPD patients showed higher expression levels. Compared with stable patients, mRNA expression level of NE (P = 0.033) in PBMCs of patients with acute exacerbation of COPD was increased. There were differences in the ratio of MMP-12/TIMP-4 in PBMC (P = 0.0055), serum (P = 0.0427), and EBC (P = 0.0035) samples between COPD patients and healthy controls. The mRNA expression of MMP-12 (r = −0.3958, P = 0.0186) and NE (r = −0.3694, P = 0.0290) in COPD patients was negatively correlated with pulmonary function. However, the mRNA expression of TIMP-4 (r = 0.2871, P = 0.0945) in PBMCs was not correlated with the FEV1 of the pulmonary function. Serum MMP-12 level was positively correlated with the MMP-12 level in EBC (P = 0.0387). The level of TIMP-4 in serum was not correlated with the level in the EBC sample (P = 0.4332). Conclusion The expression levels of MMP-12, NE, and TIMP-4 in PBMCs and serum were elevated in COPD patients. In PBMCs of COPD patients, the mRNA expression level of NE may predict acute exacerbation, and MMP-12 mRNA expression level may be used to reflect the severity of airflow limitation. However, to better assess their diagnostic or prognostic value, larger studies are necessary.

Highlights

Chronic obstructive pulmonary disease (COPD) is a heterogeneous complex disease characterized by the progressive development of airflow limitation [1]
We examined the concentrations of these mediators during acute exacerbations of COPD
We measured the release of inflammatory biomarkers from peripheral blood mononuclear cells (PBMCs) and Exhaled breath condensate (EBC) in order to investigate whether there were differences between the two subject groups

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a heterogeneous complex disease characterized by the progressive development of airflow limitation [1]. Matrix metalloproteinases (MMPs) are a family of similar proteins with similar structures that can degrade extracellular matrices, leading to structural damage and airway remodeling in COPD patients [3]. Their activity can be inhibited by TIMPs, and the balance of MMPs/TIMPs plays a major role in maintaining normal tissue structure and physiological functions. With regard to MMP-12, there have been rather few reports on the mechanisms behind the destruction of lung tissue structure, airway remodeling, and emphysema formation in patients with COPD

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Results

Conclusion