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Published on: May 21, 2021
MMP-8, MMP-9 and Neutrophil Elastase in Peripheral Blood and Exhaled Breath Condensate in COPD
JieHao Joshua Sng1,2, Silvie Prazakova2, Paul S Thomas1,2
1a Inflammation and Infection Research, School of Medical Sciences, UNSW Australia , Sydney , NSW , Australia.
Abstract:
Chronic obstructive pulmonary disease (COPD) is characterised by progressive and irreversible airflow limitation associated with chronic inflammation involving cytokines and metalloproteinases (MMPs). MMP-8, MMP-9 and neutrophil elastase (NE) are known to be implicated in COPD but the factors influencing activation and suppression remain unclear. This study aimed to compare MMP-8, MMP-9 and NE in the peripheral blood of COPD patients and controls and to likewise assess exhaled breath condensate (EBC) for these MMPs. Peripheral blood micro(mi)RNA139-5p levels, which may regulate MMPs in COPD, were also measured. Blood and EBC were collected from COPD patients (stable and during exacerbations) and healthy controls. Expression of mRNA for MMP-8, MMP-9, NE and miRNA-139-5p expression in peripheral blood mononuclear cells (PBMCs) was measured using qRT-PCR. MMP-8, MMP-9 and NE protein in plasma as well as MMP-8 and MMP-9 protein in EBC were analysed by enzyme-linked immunoassays. PBMCs from COPD patients showed greater expression of mRNA for MMP-8 (p = 0.0004), MMP-9 (p = 0.0023) and NE (p = 0.0019). PBMC expression of mRNA for NE was significantly higher in COPD exacerbations compared to stable cases (p < 0.05). Expression of mRNA for MMP-9 and NE correlated negatively with spirometry in patients (p < 0.05). Plasma from COPD patients showed greater levels of protein for MMP-8 (p = 0.003), MMP-9 (p = 0.046) and NE (p = 0.018). MMP-8 protein levels were lower in the EBC of COPD patients (p < 0.0001). In PBMCs, enhanced expression of mRNA for MMP-9 and NE is associated with COPD and may correlate with disease severity and exacerbations.
Insights
This study found increased expression of MMP-9 and neutrophil elastase mRNA in peripheral blood of chronic obstructive pulmonary disease (COPD) patients, correlating with disease severity. These findings offer insights into COPD pathogenesis and potential biomarkers.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Biochemistry
Background:
- Chronic obstructive pulmonary disease (COPD) involves progressive airflow limitation and chronic inflammation.
- Matrix metalloproteinases (MMPs) and neutrophil elastase (NE) are implicated in COPD, but their regulation is not fully understood.
- MicroRNA-139-5p may play a role in regulating MMPs in COPD.
Purpose of the Study:
- To compare levels of MMP-8, MMP-9, and NE in peripheral blood and exhaled breath condensate (EBC) of COPD patients and controls.
- To assess the expression of miRNA-139-5p in peripheral blood mononuclear cells (PBMCs) of COPD patients.
- To investigate the relationship between these markers, disease severity, and exacerbations.
Main Methods:
- Collected blood and EBC from stable COPD patients, COPD patients during exacerbations, and healthy controls.
- Measured mRNA expression of MMP-8, MMP-9, NE, and miRNA-139-5p in PBMCs using qRT-PCR.
- Quantified MMP-8, MMP-9, and NE protein in plasma and MMP-8, MMP-9 protein in EBC using enzyme-linked immunoassays.
Main Results:
- COPD patients exhibited significantly higher mRNA expression for MMP-8, MMP-9, and NE in PBMCs compared to controls.
- NE mRNA expression was higher during COPD exacerbations than in stable COPD.
- mRNA expression of MMP-9 and NE correlated negatively with spirometry results in COPD patients.
- Plasma levels of MMP-8, MMP-9, and NE proteins were elevated in COPD patients.
- MMP-8 protein levels were lower in the EBC of COPD patients.
Conclusions:
- Enhanced mRNA expression of MMP-9 and NE in PBMCs is associated with COPD.
- These elevated markers may correlate with COPD disease severity and exacerbations.
- Further research into miRNA-139-5p regulation of MMPs could provide therapeutic targets for COPD.
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