Lipopolysaccharide does not alter small airway reactivity in mouse lung slices

Donovan, C, Royce, S, Vlahos, R and Bourke, J 2015, 'Lipopolysaccharide does not alter small airway reactivity in mouse lung slices', PLOS One, pp. 1-16.


Document type: Journal Article
Collection: Journal Articles

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Title Lipopolysaccharide does not alter small airway reactivity in mouse lung slices
Author(s) Donovan, C
Royce, S
Vlahos, R
Bourke, J
Year 2015
Journal name PLOS One
Start page 1
End page 16
Total pages 16
Publisher Public Library of Science
Abstract The bacterial endotoxin, lipopolysaccharide (LPS) has been associated with occupational airway diseases with asthma-like symptoms and in acute exacerbations of COPD. The direct and indirect effects of LPS on small airway reactivity have not been fully elucidated. We tested the hypothesis that both in vitro and in vivo LPS treatment would increase contraction and impair relaxation of mouse small airways. Lung slices were prepared from naïve Balb/C mice and cultured in the absence or presence of LPS (10 µg/ml) for up to 48 h for measurement of TNFα levels in conditioned media. Alternatively, mice were challenged with PBS or LPS in vivo once a day for 4 days for preparation of lung slices or for harvest of lungs for Q-PCR analysis of gene expression of pro-inflammatory cytokines and receptors involved in airway contraction. Reactivity of small airways to contractile agonists, methacholine and serotonin, and bronchodilator agents, salbutamol, isoprenaline and rosiglitazone, were assessed using phase-contrast microscopy. In vitro LPS treatment of slices increased TNFα release 6-fold but did not alter contraction or relaxation to any agonists tested. In vivo LPS treatment increased lung gene expression of TNFα, IL-1β and ryanodine receptor isoform 2 more than 5-fold. However there were no changes in reactivity in lung slices from these mice, even when also incubated with LPS ex vivo. Despite evidence of LPS-induced inflammation, neither airway hyperresponsiveness or impaired dilator reactivity were evident. The increase in ryanodine receptor isoform 2, known to regulate calcium signaling in vascular smooth muscle, warrants investigation. Since LPS failed to elicit changes in small airway reactivity in mouse lung slices following in vitro or in vivo treatment, alternative approaches are required to define the potential contribution of this endotoxin to altered small airway reactivity in human lung diseases.
Subject Respiratory Diseases
Keyword(s) Inflammation
Cytokines
Gene expression
Bronchodilators
Inflammatory diseases
Chronic obstructive pulmonary disease
Endotoxins
Smooth muscles
DOI - identifier 10.1371/journal.pone.0122069
Copyright notice © 2015 Donovan et al
ISSN 1932-6203
Additional Notes Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
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