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

Abstract

BackgroundChronic 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.MethodsPPARγ 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.ResultsPPARγ 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.ConclusionPPARγ 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.

Altered expression of leptin and leptin receptor in the development of immune‑mediated aplastic anemia in mice

“…The thermocycling conditions were as follows: 1 cycle of 50°C for 2 min and 95°C for 10 min, followed by 40 cycles of 95°C for 30 sec and 60°C for 30 sec. The data was analyzed with 2 −ΔΔCt (23). The primers used for β-actin, LEP, LEP-R, CCAAT/enhancer-binding protein (C/EBP)α, peroxisome proliferator-activated receptor γ (PPARγ) and runt-related transcription factor 2 (Runx2) are listed in Table I.…”

FOXK2 targeting by the SCF-E3 ligase subunit FBXO24 for ubiquitin mediated degradation modulates mitochondrial respiration

“…The bacterial pathogen, Pseudomonas aeruginosa manipulates host transcription factors to facilitate infection and evasion of host immune responses to modulate its virulence ( 8 , 13 , 14 ). These effects of P. aeruginosa, in part, involve regulating activities of hypoxia-inducible factor-1α ( 15 , 16 ) or peroxisome proliferator-activated receptor gamma (PPAR-γ) ( 16 , 17 , 18 , 19 ) to promote a more favorable environment for bacterial survival and replication within host cells ( 14 ). The effect of microbial actions on many transcriptional networks requires further investigation.…”