Cargando…

Inhaled dsRNA and rhinovirus evoke neutrophilic exacerbation and lung expression of thymic stromal lymphopoietin in allergic mice with established experimental asthma

BACKGROUND: Rhinovirus infection or dsRNA stimulation increased thymic stromal lymphopoietin (TSLP), an upstream pro-allergic cytokine, in asthmatic bronchial epithelial cells. We hypothesized that dsRNA challenges superimposed on established experimental allergic asthma constitute a useful exacerba...

Descripción completa

Detalles Bibliográficos
Autores principales: Mahmutovic-Persson, I, Akbarshahi, H, Bartlett, N W, Glanville, N, Johnston, S L, Brandelius, A, Uller, L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223976/
https://www.ncbi.nlm.nih.gov/pubmed/24283976
http://dx.doi.org/10.1111/all.12329
_version_ 1782343291287633920
author Mahmutovic-Persson, I
Akbarshahi, H
Bartlett, N W
Glanville, N
Johnston, S L
Brandelius, A
Uller, L
author_facet Mahmutovic-Persson, I
Akbarshahi, H
Bartlett, N W
Glanville, N
Johnston, S L
Brandelius, A
Uller, L
author_sort Mahmutovic-Persson, I
collection PubMed
description BACKGROUND: Rhinovirus infection or dsRNA stimulation increased thymic stromal lymphopoietin (TSLP), an upstream pro-allergic cytokine, in asthmatic bronchial epithelial cells. We hypothesized that dsRNA challenges superimposed on established experimental allergic asthma constitute a useful exacerbation model. We further hypothesized that TSLP is induced at dsRNA- and rhinoviral infection-induced exacerbations. METHODS: Allergic mice were challenged with OVA followed by three daily intranasal challenges with dsRNA or saline. Bronchoalveolar lavage fluid (BALF) was analysed for total protein, lactate dehydrogenase (LDH), CXCL1/KC, CCL2/MCP-1 and differential cell counts. Lung tissue histology, neutrophils and TSLP, TNF-α, IFN-β and IFN-λ mRNA were examined. Alternatively, allergen-challenged mice received intranasal rhinovirus-(RV)-1B followed by lung TSLP immunostaining. RESULTS: In mice with allergic airway inflammation, dsRNA challenges caused a significant exacerbation increasing lung tissue inflammation score and tissue neutrophilia. Bronchoalveolar lavage fluid neutrophils, total protein, LDH, CXCL1/KC and CCL2/MCP-1 were also increased (P < 0.01), and so were lung tissue expressions of TNF-α, IFN-λ and TSLP (P < 0.01), but IFN-β was not increased. TSLP, IFN-λ and LDH were not increased by allergen or dsRNA challenges alone, but increased exclusively at exacerbations. RV1B infection-induced exacerbation also increased lung tissue TSLP (P < 0.05). CONCLUSIONS: dsRNA-induced exacerbation in mice with experimental asthma involved general inflammation, cytokines and interferons, in agreement with previous observations in exacerbating human asthma. Additionally, both dsRNA and RV1B infection increased lung TSLP exclusively at exacerbations. Our data suggest that dsRNA challenges superimposed on allergic inflammation are suited for pharmacological studies of asthma exacerbations including the regulation of lung tissue TSLP, TNF-α, IFN-β and IFN-λ.
format Online
Article
Text
id pubmed-4223976
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Blackwell Publishing Ltd
record_format MEDLINE/PubMed
spelling pubmed-42239762014-11-20 Inhaled dsRNA and rhinovirus evoke neutrophilic exacerbation and lung expression of thymic stromal lymphopoietin in allergic mice with established experimental asthma Mahmutovic-Persson, I Akbarshahi, H Bartlett, N W Glanville, N Johnston, S L Brandelius, A Uller, L Allergy Original Articles BACKGROUND: Rhinovirus infection or dsRNA stimulation increased thymic stromal lymphopoietin (TSLP), an upstream pro-allergic cytokine, in asthmatic bronchial epithelial cells. We hypothesized that dsRNA challenges superimposed on established experimental allergic asthma constitute a useful exacerbation model. We further hypothesized that TSLP is induced at dsRNA- and rhinoviral infection-induced exacerbations. METHODS: Allergic mice were challenged with OVA followed by three daily intranasal challenges with dsRNA or saline. Bronchoalveolar lavage fluid (BALF) was analysed for total protein, lactate dehydrogenase (LDH), CXCL1/KC, CCL2/MCP-1 and differential cell counts. Lung tissue histology, neutrophils and TSLP, TNF-α, IFN-β and IFN-λ mRNA were examined. Alternatively, allergen-challenged mice received intranasal rhinovirus-(RV)-1B followed by lung TSLP immunostaining. RESULTS: In mice with allergic airway inflammation, dsRNA challenges caused a significant exacerbation increasing lung tissue inflammation score and tissue neutrophilia. Bronchoalveolar lavage fluid neutrophils, total protein, LDH, CXCL1/KC and CCL2/MCP-1 were also increased (P < 0.01), and so were lung tissue expressions of TNF-α, IFN-λ and TSLP (P < 0.01), but IFN-β was not increased. TSLP, IFN-λ and LDH were not increased by allergen or dsRNA challenges alone, but increased exclusively at exacerbations. RV1B infection-induced exacerbation also increased lung tissue TSLP (P < 0.05). CONCLUSIONS: dsRNA-induced exacerbation in mice with experimental asthma involved general inflammation, cytokines and interferons, in agreement with previous observations in exacerbating human asthma. Additionally, both dsRNA and RV1B infection increased lung TSLP exclusively at exacerbations. Our data suggest that dsRNA challenges superimposed on allergic inflammation are suited for pharmacological studies of asthma exacerbations including the regulation of lung tissue TSLP, TNF-α, IFN-β and IFN-λ. Blackwell Publishing Ltd 2014-03 2013-11-28 /pmc/articles/PMC4223976/ /pubmed/24283976 http://dx.doi.org/10.1111/all.12329 Text en © 2013 The Authors. Allergy published by John Wiley & Sons Ltd http://creativecommons.org/licenses/by-nc/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Mahmutovic-Persson, I
Akbarshahi, H
Bartlett, N W
Glanville, N
Johnston, S L
Brandelius, A
Uller, L
Inhaled dsRNA and rhinovirus evoke neutrophilic exacerbation and lung expression of thymic stromal lymphopoietin in allergic mice with established experimental asthma
title Inhaled dsRNA and rhinovirus evoke neutrophilic exacerbation and lung expression of thymic stromal lymphopoietin in allergic mice with established experimental asthma
title_full Inhaled dsRNA and rhinovirus evoke neutrophilic exacerbation and lung expression of thymic stromal lymphopoietin in allergic mice with established experimental asthma
title_fullStr Inhaled dsRNA and rhinovirus evoke neutrophilic exacerbation and lung expression of thymic stromal lymphopoietin in allergic mice with established experimental asthma
title_full_unstemmed Inhaled dsRNA and rhinovirus evoke neutrophilic exacerbation and lung expression of thymic stromal lymphopoietin in allergic mice with established experimental asthma
title_short Inhaled dsRNA and rhinovirus evoke neutrophilic exacerbation and lung expression of thymic stromal lymphopoietin in allergic mice with established experimental asthma
title_sort inhaled dsrna and rhinovirus evoke neutrophilic exacerbation and lung expression of thymic stromal lymphopoietin in allergic mice with established experimental asthma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223976/
https://www.ncbi.nlm.nih.gov/pubmed/24283976
http://dx.doi.org/10.1111/all.12329
work_keys_str_mv AT mahmutovicperssoni inhaleddsrnaandrhinovirusevokeneutrophilicexacerbationandlungexpressionofthymicstromallymphopoietininallergicmicewithestablishedexperimentalasthma
AT akbarshahih inhaleddsrnaandrhinovirusevokeneutrophilicexacerbationandlungexpressionofthymicstromallymphopoietininallergicmicewithestablishedexperimentalasthma
AT bartlettnw inhaleddsrnaandrhinovirusevokeneutrophilicexacerbationandlungexpressionofthymicstromallymphopoietininallergicmicewithestablishedexperimentalasthma
AT glanvillen inhaleddsrnaandrhinovirusevokeneutrophilicexacerbationandlungexpressionofthymicstromallymphopoietininallergicmicewithestablishedexperimentalasthma
AT johnstonsl inhaleddsrnaandrhinovirusevokeneutrophilicexacerbationandlungexpressionofthymicstromallymphopoietininallergicmicewithestablishedexperimentalasthma
AT brandeliusa inhaleddsrnaandrhinovirusevokeneutrophilicexacerbationandlungexpressionofthymicstromallymphopoietininallergicmicewithestablishedexperimentalasthma
AT ullerl inhaleddsrnaandrhinovirusevokeneutrophilicexacerbationandlungexpressionofthymicstromallymphopoietininallergicmicewithestablishedexperimentalasthma