Hypoxia and sterile inflammation in cystic fibrosis airways: Mechanisms and potential therapies

Copyright © ERS 2017. Cystic fibrosis is one of the most common autosomal recessive genetic diseases in Caucasian populations. Diagnosis via newborn screening and targeted nutritional and antibiotic therapy have improved outcomes, however respiratory failure remains the key cause of morbidity and m...

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Main Authors: Montgomery, S.T., Mall, M.A., Kicic, Anthony, Stick, S.M.
Format: Journal Article
Language:English
Published: EUROPEAN RESPIRATORY SOC JOURNALS LTD 2017
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/76811
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author Montgomery, S.T.
Mall, M.A.
Kicic, Anthony
Stick, S.M.
author_facet Montgomery, S.T.
Mall, M.A.
Kicic, Anthony
Stick, S.M.
author_sort Montgomery, S.T.
building Curtin Institutional Repository
collection Online Access
description Copyright © ERS 2017. Cystic fibrosis is one of the most common autosomal recessive genetic diseases in Caucasian populations. Diagnosis via newborn screening and targeted nutritional and antibiotic therapy have improved outcomes, however respiratory failure remains the key cause of morbidity and mortality. Progressive respiratory disease in cystic fibrosis is characterised by chronic neutrophilic airway inflammation associated with structural airway damage leading to bronchiectasis and decreased lung function. Mucus obstruction is a characteristic early abnormality in the cystic fibrosis airway, associated with neutrophilic inflammation often in the absence of detectable infection. Recent studies have suggested a link between hypoxic cell death and sterile neutrophilic inflammation in cystic fibrosis and other diseases via the IL-1 signalling pathway. In this review, we consider recent evidence regarding the cellular responses to respiratory hypoxia as a potential driver of sterile neutrophilic inflammation in the lung, current knowledge on hypoxia as a pathogenic mechanism in cystic fibrosis and the potential for current and future therapies to alleviate hypoxia-driven sterile inflammation.
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spelling curtin-20.500.11937-768112019-11-11T07:16:37Z Hypoxia and sterile inflammation in cystic fibrosis airways: Mechanisms and potential therapies Montgomery, S.T. Mall, M.A. Kicic, Anthony Stick, S.M. Science & Technology Life Sciences & Biomedicine Respiratory System NF-KAPPA-B TRANSMEMBRANE CONDUCTANCE REGULATOR INDUCIBLE FACTOR-I INTERLEUKIN-1 RECEPTOR ANTAGONIST ALVEOLAR EPITHELIAL-CELLS OXYGEN PARTIAL-PRESSURE LUNG-DISEASE PSEUDOMONAS-AERUGINOSA NLRP3 INFLAMMASOME HYPERTONIC SALINE Copyright © ERS 2017. Cystic fibrosis is one of the most common autosomal recessive genetic diseases in Caucasian populations. Diagnosis via newborn screening and targeted nutritional and antibiotic therapy have improved outcomes, however respiratory failure remains the key cause of morbidity and mortality. Progressive respiratory disease in cystic fibrosis is characterised by chronic neutrophilic airway inflammation associated with structural airway damage leading to bronchiectasis and decreased lung function. Mucus obstruction is a characteristic early abnormality in the cystic fibrosis airway, associated with neutrophilic inflammation often in the absence of detectable infection. Recent studies have suggested a link between hypoxic cell death and sterile neutrophilic inflammation in cystic fibrosis and other diseases via the IL-1 signalling pathway. In this review, we consider recent evidence regarding the cellular responses to respiratory hypoxia as a potential driver of sterile neutrophilic inflammation in the lung, current knowledge on hypoxia as a pathogenic mechanism in cystic fibrosis and the potential for current and future therapies to alleviate hypoxia-driven sterile inflammation. 2017 Journal Article http://hdl.handle.net/20.500.11937/76811 10.1183/13993003.00903-2016 English EUROPEAN RESPIRATORY SOC JOURNALS LTD restricted
spellingShingle Science & Technology
Life Sciences & Biomedicine
Respiratory System
NF-KAPPA-B
TRANSMEMBRANE CONDUCTANCE REGULATOR
INDUCIBLE FACTOR-I
INTERLEUKIN-1 RECEPTOR ANTAGONIST
ALVEOLAR EPITHELIAL-CELLS
OXYGEN PARTIAL-PRESSURE
LUNG-DISEASE
PSEUDOMONAS-AERUGINOSA
NLRP3 INFLAMMASOME
HYPERTONIC SALINE
Montgomery, S.T.
Mall, M.A.
Kicic, Anthony
Stick, S.M.
Hypoxia and sterile inflammation in cystic fibrosis airways: Mechanisms and potential therapies
title Hypoxia and sterile inflammation in cystic fibrosis airways: Mechanisms and potential therapies
title_full Hypoxia and sterile inflammation in cystic fibrosis airways: Mechanisms and potential therapies
title_fullStr Hypoxia and sterile inflammation in cystic fibrosis airways: Mechanisms and potential therapies
title_full_unstemmed Hypoxia and sterile inflammation in cystic fibrosis airways: Mechanisms and potential therapies
title_short Hypoxia and sterile inflammation in cystic fibrosis airways: Mechanisms and potential therapies
title_sort hypoxia and sterile inflammation in cystic fibrosis airways: mechanisms and potential therapies
topic Science & Technology
Life Sciences & Biomedicine
Respiratory System
NF-KAPPA-B
TRANSMEMBRANE CONDUCTANCE REGULATOR
INDUCIBLE FACTOR-I
INTERLEUKIN-1 RECEPTOR ANTAGONIST
ALVEOLAR EPITHELIAL-CELLS
OXYGEN PARTIAL-PRESSURE
LUNG-DISEASE
PSEUDOMONAS-AERUGINOSA
NLRP3 INFLAMMASOME
HYPERTONIC SALINE
url http://hdl.handle.net/20.500.11937/76811