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Citation
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HERO ID
3456722
Reference Type
Journal Article
Title
Combining an epithelial repair factor and anti-fibrotic with a corticosteroid offers optimal treatment for allergic airways disease
Author(s)
Patel, KP; Giraud, AS; Samuel, CS; Royce, SG
Year
2016
Is Peer Reviewed?
Yes
Journal
British Journal of Pharmacology
ISSN:
0007-1188
EISSN:
1476-5381
Volume
173
Issue
12
Page Numbers
2016-2029
Language
English
PMID
27060978
DOI
10.1111/bph.13494
Web of Science Id
WOS:000377252200010
URL
http://doi.wiley.com/10.1111/bph.13494
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Abstract
Background and Purpose We evaluated the extent to which individual versus combination treatments that specifically target airway epithelial damage [trefoil factor-2 (TFF2)], airway fibrosis [serelaxin (RLX)] or airway inflammation [dexamethasone (DEX)] reversed the pathogenesis of chronic allergic airways disease (AAD). Experimental Approach Following induction of ovalbumin (OVA)-induced chronic AAD in 6-8 week female Balb/c mice, animals were i.p. administered naphthalene (NA) on day 64 to induce epithelial damage, then received daily intranasal administration of RLX (0.8 mg·mL-1), TFF2 (0.5 mg·mL-1), DEX (0.5 mg·mL-1), RLX + TFF2 or RLX + TFF2 + DEX from days 67-74. On day 75, lung function was assessed by invasive plethysmography, before lung tissue was isolated for analyses of various measures. The control group was treated with saline + corn oil (vehicle for NA). Key Results OVA + NA-injured mice demonstrated significantly increased airway inflammation, airway remodelling (AWR) (epithelial damage/thickness; subepithelial myofibroblast differentiation, extracellular matrix accumulation and fibronectin deposition; total lung collagen concentration), and significantly reduced airway dynamic compliance (cDyn). RLX + TFF2 markedly reversed several measures of OVA + NA-induced AWR and normalized the reduction in cDyn. The combined effects of RLX + TFF2 + DEX significantly reversed peribronchial inflammation score, airway epithelial damage, subepithelial extracellular matrix accumulation/fibronectin deposition and total lung collagen concentration (by 50-90%) and also normalized the reduction of cDyn. Conclusions and Implications Combining an epithelial repair factor and anti-fibrotic provides an effective means of treating the AWR and dysfunction associated with AAD/asthma and may act as an effective adjunct therapy to anti-inflammatory corticosteroids. © 2016 The British Pharmacological Society.
Tags
IRIS
•
Naphthalene
Database searches - Jan 2017 (private)
New Jan 2017 (private)
Database Searches
WOS
Combined data set
Data set for title/abstract screening
Data set for full text review
Excluded – PECO criteria not met (full-text)
Supplemental material
Non-PECO routes of exposure
Other
•
Mouse Lung Tumor Workshop 2014
Mouse Lung Tumor Initial Search Sept-Oct 2023
PubMed
WoS
•
Naphthalene (2021 Evidence mapping publication)
Database searches - Jan 2017 (private)
New Jan 2017 (private)
Database Searches
WOS
Combined data set
Data set for title/abstract screening
Data set for full text review
Excluded – PECO criteria not met (full-text)
Supplemental material
Exposure routes other than inhalation, oral, or dermal (animal studies)
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