Compartmental and temporal dynamics of chronic inflammation and airway remodelling in a chronic asthma mouse model.

<h4>Background</h4>Allergic asthma is associated with chronic airway inflammation and progressive airway remodelling. However, the dynamics of the development of these features and their spontaneous and pharmacological reversibility are still poorly understood. We have therefore investig...

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Autores principales:	Mohammed Alrifai, Leigh M Marsh, Tanja Dicke, Ayse Kılıç, Melanie L Conrad, Harald Renz, Holger Garn
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a520367d8deb4954a0ff84bc9575161c
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spelling	oai:doaj.org-article:a520367d8deb4954a0ff84bc9575161c2021-11-18T08:36:56ZCompartmental and temporal dynamics of chronic inflammation and airway remodelling in a chronic asthma mouse model.1932-620310.1371/journal.pone.0085839https://doaj.org/article/a520367d8deb4954a0ff84bc9575161c2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24465740/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Allergic asthma is associated with chronic airway inflammation and progressive airway remodelling. However, the dynamics of the development of these features and their spontaneous and pharmacological reversibility are still poorly understood. We have therefore investigated the dynamics of airway remodelling and repair in an experimental asthma model and studied how pharmacological intervention affects these processes.<h4>Methods</h4>Using BALB/c mice, the kinetics of chronic asthma progression and resolution were characterised in absence and presence of inhaled corticosteroid (ICS) treatment. Airway inflammation and remodelling was assessed by the analysis of bronchoalveolar and peribronichal inflammatory cell infiltrate, goblet cell hyperplasia, collagen deposition and smooth muscle thickening.<h4>Results</h4>Chronic allergen exposure resulted in early (goblet cell hyperplasia) and late remodelling (collagen deposition and smooth muscle thickening). After four weeks of allergen cessation eosinophilic inflammation, goblet cell hyperplasia and collagen deposition were resolved, full resolution of lymphocyte inflammation and smooth muscle thickening was only observed after eight weeks. ICS therapy when started before the full establishment of chronic asthma reduced the development of lung inflammation, decreased goblet cell hyperplasia and collagen deposition, but did not affect smooth muscle thickening. These effects of ICS on airway remodelling were maintained for a further four weeks even when therapy was discontinued.<h4>Conclusions</h4>Utilising a chronic model of experimental asthma we have shown that repeated allergen exposure induces reversible airway remodelling and inflammation in mice. Therapeutic intervention with ICS was partially effective in inhibiting the transition from acute to chronic asthma by reducing airway inflammation and remodelling but was ineffective in preventing smooth muscle hypertrophy.Mohammed AlrifaiLeigh M MarshTanja DickeAyse KılıçMelanie L ConradHarald RenzHolger GarnPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e85839 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mohammed Alrifai Leigh M Marsh Tanja Dicke Ayse Kılıç Melanie L Conrad Harald Renz Holger Garn Compartmental and temporal dynamics of chronic inflammation and airway remodelling in a chronic asthma mouse model.
description	<h4>Background</h4>Allergic asthma is associated with chronic airway inflammation and progressive airway remodelling. However, the dynamics of the development of these features and their spontaneous and pharmacological reversibility are still poorly understood. We have therefore investigated the dynamics of airway remodelling and repair in an experimental asthma model and studied how pharmacological intervention affects these processes.<h4>Methods</h4>Using BALB/c mice, the kinetics of chronic asthma progression and resolution were characterised in absence and presence of inhaled corticosteroid (ICS) treatment. Airway inflammation and remodelling was assessed by the analysis of bronchoalveolar and peribronichal inflammatory cell infiltrate, goblet cell hyperplasia, collagen deposition and smooth muscle thickening.<h4>Results</h4>Chronic allergen exposure resulted in early (goblet cell hyperplasia) and late remodelling (collagen deposition and smooth muscle thickening). After four weeks of allergen cessation eosinophilic inflammation, goblet cell hyperplasia and collagen deposition were resolved, full resolution of lymphocyte inflammation and smooth muscle thickening was only observed after eight weeks. ICS therapy when started before the full establishment of chronic asthma reduced the development of lung inflammation, decreased goblet cell hyperplasia and collagen deposition, but did not affect smooth muscle thickening. These effects of ICS on airway remodelling were maintained for a further four weeks even when therapy was discontinued.<h4>Conclusions</h4>Utilising a chronic model of experimental asthma we have shown that repeated allergen exposure induces reversible airway remodelling and inflammation in mice. Therapeutic intervention with ICS was partially effective in inhibiting the transition from acute to chronic asthma by reducing airway inflammation and remodelling but was ineffective in preventing smooth muscle hypertrophy.
format	article
author	Mohammed Alrifai Leigh M Marsh Tanja Dicke Ayse Kılıç Melanie L Conrad Harald Renz Holger Garn
author_facet	Mohammed Alrifai Leigh M Marsh Tanja Dicke Ayse Kılıç Melanie L Conrad Harald Renz Holger Garn
author_sort	Mohammed Alrifai
title	Compartmental and temporal dynamics of chronic inflammation and airway remodelling in a chronic asthma mouse model.
title_short	Compartmental and temporal dynamics of chronic inflammation and airway remodelling in a chronic asthma mouse model.
title_full	Compartmental and temporal dynamics of chronic inflammation and airway remodelling in a chronic asthma mouse model.
title_fullStr	Compartmental and temporal dynamics of chronic inflammation and airway remodelling in a chronic asthma mouse model.
title_full_unstemmed	Compartmental and temporal dynamics of chronic inflammation and airway remodelling in a chronic asthma mouse model.
title_sort	compartmental and temporal dynamics of chronic inflammation and airway remodelling in a chronic asthma mouse model.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/a520367d8deb4954a0ff84bc9575161c
work_keys_str_mv	AT mohammedalrifai compartmentalandtemporaldynamicsofchronicinflammationandairwayremodellinginachronicasthmamousemodel AT leighmmarsh compartmentalandtemporaldynamicsofchronicinflammationandairwayremodellinginachronicasthmamousemodel AT tanjadicke compartmentalandtemporaldynamicsofchronicinflammationandairwayremodellinginachronicasthmamousemodel AT aysekılıc compartmentalandtemporaldynamicsofchronicinflammationandairwayremodellinginachronicasthmamousemodel AT melanielconrad compartmentalandtemporaldynamicsofchronicinflammationandairwayremodellinginachronicasthmamousemodel AT haraldrenz compartmentalandtemporaldynamicsofchronicinflammationandairwayremodellinginachronicasthmamousemodel AT holgergarn compartmentalandtemporaldynamicsofchronicinflammationandairwayremodellinginachronicasthmamousemodel
_version_	1718421579040292864

Compartmental and temporal dynamics of chronic inflammation and airway remodelling in a chronic asthma mouse model.

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