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

Lucy Burr, Geraint Rogers, Alice Chen, Steven Taylor, Simon Bowler, Rebecca Keating, Megan Martin, Sumaira Hasnain, Michael McGuckin

Research output: Contribution to journalArticle

Abstract

Background 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 hypothe-sised 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. Methods 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. Results 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<0.001, Mann-Whitney U test). This lower PPARγ expression correlated negatively with Pseudomonas aeruginosa (r = -0.53, n = 31; p = 0.002). No significant association was seen between PPARγ and total bacterial levels or levels Haemophilus influenzae. Conclusion PPARγ is expressed in low levels in the airways of non-CF bronchiectasis subjects, despite an aggressive inflammatory response. This low level PPARγ expression is particularly associated with the presence of high levels of P. aeruginosa, and may represent an intrinsic link with this bacterial pathogen.

Original languageEnglish
Article numbere0202296
Number of pages12
JournalPLoS One
Volume13
Issue number8
DOIs
Publication statusPublished - 2018

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