title: MMP-8, MMP-9 and Neutrophil Elastase in Peripheral Blood and Exhaled Breath Condensate in COPD.
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.
authors.affiliation: a Inflammation and Infection Research, School of Medical Sciences, UNSW Australia , Sydney , NSW , Australia.|b Department of Respiratory Medicine , Prince of Wales Hospital , Randwick , NSW , Australia.
authors.forename: JieHao Joshua
authors.initials: JJ
authors.lastname: Sng
authors.affiliation: b Department of Respiratory Medicine , Prince of Wales Hospital , Randwick , NSW , Australia.
authors.forename: Silvie
authors.initials: S
authors.lastname: Prazakova
authors.affiliation: a Inflammation and Infection Research, School of Medical Sciences, UNSW Australia , Sydney , NSW , Australia.|b Department of Respiratory Medicine , Prince of Wales Hospital , Randwick , NSW , Australia.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Thomas
authors.affiliation: a Inflammation and Infection Research, School of Medical Sciences, UNSW Australia , Sydney , NSW , Australia.
authors.forename: Cristan
authors.initials: C
authors.lastname: Herbert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D001944:Breath Tests; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000201:enzymology*; D012333:RNA, Messenger / Q000097:blood*; D012720:Severity of Illness Index; D013147:Spirometry
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D019272:Leukocyte Elastase; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: COPD; MMP-8; MMP-9; exhaled breath condensate; neutrophil elastase