Pattern of Expression of Genes Involved in Systemic Inflammation and Glutathione Metabolism Reveals Exacerbation of COPD

Abstract

To test the hypothesis that they serve as systemic biomarkers of chronic obstructive pulmonary disease (COPD), we profiled the mRNA expression of enzymes connected to systemic inflammation and GSH metabolism in peripheral blood mononuclear cells (PBMCs). These were taken from patients displaying acute exacerbation of COPD (AE-COPD) and stable COPD, and also from non-obstructive smokers and non-smokers. The expression of poly(ADP-ribose) polymerase-1 was increased, but that of histone deacetylase 2 was decreased in association with AE-COPD. The expression of modulatory subunit of glutamyl–cysteine ligase was higher and that of its catalytic subunit, together with the expression of dipeptidyl peptidase 4, was lower in COPD patients compared with non-obstructive smokers and non-smokers. Leukotriene A4 hydrolase saw increased expression in patients with COPD according to disease severity compared to non-obstructive individuals, whereas the expression of GSH peroxidase increased in non-obstructive smokers and COPD patients with the growing number of pack-years smoked. The results corroborate COPD and its acute exacerbation as a complex systemic disorder demonstrating distinct associations with the expression of enzymes linked to inflammation and the regulation of GSH metabolism.

Keywords

• COPD
• COPD exacerbation
• oxidative stress
• glutathione
• metabolism
• systemic inflammation