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PPARγ is reduced in the airways of non-CF bronchiectasis subjects and is inversely correlated with the presence of Pseudomonas aeruginosa.
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.
Afiliación
  • Burr LD; Immunity, Infection and Inflammation Program, Mater Research-University of Queensland, Translational Research Institute, Wooloongabba, QLD, Australia.
  • Rogers GB; Department of Respiratory Medicine, Mater Misericordiae Brisbane Ltd, South Brisbane, QLD, Australia.
  • Chen AC; SAHMRI Infection and Immunity Theme, School of Medicine, Flinders University, Adelaide, Australia.
  • Taylor SL; Immunity, Infection and Inflammation Program, Mater Research-University of Queensland, Translational Research Institute, Wooloongabba, QLD, Australia.
  • Bowler SD; SAHMRI Infection and Immunity Theme, School of Medicine, Flinders University, Adelaide, Australia.
  • Keating RL; Department of Respiratory Medicine, Mater Misericordiae Brisbane Ltd, South Brisbane, QLD, Australia.
  • Martin ML; Department of Respiratory Medicine, Mater Misericordiae Brisbane Ltd, South Brisbane, QLD, Australia.
  • Hasnain SZ; Department of Respiratory Medicine, Mater Misericordiae Brisbane Ltd, South Brisbane, QLD, Australia.
  • McGuckin MA; Immunity, Infection and Inflammation Program, Mater Research-University of Queensland, Translational Research Institute, Wooloongabba, QLD, Australia.
PLoS One ; 13(8): e0202296, 2018.
Article en En | MEDLINE | ID: mdl-30114278
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 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. 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Bronquiectasia / Líquido del Lavado Bronquioalveolar / PPAR gamma Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Bronquiectasia / Líquido del Lavado Bronquioalveolar / PPAR gamma Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos