PPARγ is reduced in the airways of non-CF bronchiectasis subjects and is inversely correlated with the presence of Pseudomonas aeruginosa

• Published in: PloS one 2018-08, Vol.13 (8), p.e0202296-e0202296
• Main Authors: Burr, Lucy D, Rogers, Geraint B, Chen, Alice C-H, Taylor, Steven L, Bowler, Simon D, Keating, Rebecca L, Martin, Megan L, Hasnain, Sumaira Z, McGuckin, Michael A
• Format: Article
• Language: English
• Subjects: Adult; Alveoli; Bacteria; Bacterial Load; Biology and Life Sciences; Bronchiectasis; Bronchiectasis - immunology; Bronchiectasis - microbiology; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Bronchoalveolar Lavage Fluid - microbiology; Bronchus; Cystic fibrosis; Deoxyribonucleic acid; DNA; Down-regulation; Female; Gene expression; Gene Expression Regulation; Humans; Infections; Inflammation; Inflammatory response; Leukocytes (neutrophilic); Ligands; Low level; Male; Medicine; Medicine and Health Sciences; Middle Aged; PPAR gamma - metabolism; Pseudomonas aeruginosa; Pseudomonas aeruginosa - genetics; Research and analysis methods; Respiratory tract; Respiratory tract diseases; Ribonucleic acid; RNA; rRNA 16S; Sputum
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0202296

Chronic airway inflammation in conditions such as cystic fibrosis (CF) and non-CF bronchiectasis is characterised by a predominant neutrophilic inflammatory response, commonly due to the presence of pathogenic bacteria such as Pseudomonas aeruginosa. We hypothesised that down-regulation of the anti-inflammatory nuclear transcription regulator peroxisome proliferator-activated receptor gamma (PPARγ in non-CF bronchiectasis subjects may explain why this exuberant neutrophilic inflammation is able to persist unchecked in the inflamed airway. PPARγ gene expression was assessed in bronchoalveolar lavage fluid (BAL) of 35 macrolide naïve non-CF bronchiectasis subjects and compared with that in 20 healthy controls. Human RNA was extracted from pelleted BAL and PPARγ expression was determined by reverse-transcription quantitative PCR. Bacterial DNA was extracted from paired induced sputum and total bacterial load was determined by 16S rRNA qPCR. Quantification of individual bacterial species was achieved by qPCR. PPARγ expression was lower in subjects with non-CF bronchiectasis compared with healthy control subjects (control: 1.00, IQR 0.55-1.44, n = 20 vs. Bronchiectasis: 0.49, IQR 0.12-0.89; n = 35; p