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CYSTATHIONINE γ-LYASE DEFICIENCY ENHANCES AIRWAY REACTIVITY AND VIRAL-INDUCED DISEASE IN MICE EXPOSED TO SIDE-STREAM TOBACCO SMOKE

BACKGROUND: Environmental tobacco smoke (ETS) is a known risk factor for severe respiratory syncytial virus (RSV) infections, yet the mechanisms of ETS/RSV co-morbidity are largely unknown. Cystathionine γ-lyase regulates important physiological functions of the respiratory tract. METHODS: We used m...

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Autores principales: Ivanciuc, Teodora, Sbrana, Elena, Casola, Antonella, Garofalo, Roberto P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594876/
https://www.ncbi.nlm.nih.gov/pubmed/30986815
http://dx.doi.org/10.1038/s41390-019-0396-6
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author Ivanciuc, Teodora
Sbrana, Elena
Casola, Antonella
Garofalo, Roberto P.
author_facet Ivanciuc, Teodora
Sbrana, Elena
Casola, Antonella
Garofalo, Roberto P.
author_sort Ivanciuc, Teodora
collection PubMed
description BACKGROUND: Environmental tobacco smoke (ETS) is a known risk factor for severe respiratory syncytial virus (RSV) infections, yet the mechanisms of ETS/RSV co-morbidity are largely unknown. Cystathionine γ-lyase regulates important physiological functions of the respiratory tract. METHODS: We used mice genetically deficient in the cystathionine γ-lyase enzyme (CSE), the major H(2)S-generating enzyme in the lung to determine the contribution of H(2)S to airway disease in response to side-stream tobacco smoke (TS), and to TS /RSV co-exposure. RESULTS: Following a two-week period of exposure to TS, CSE-deficient mice (KO) showed a dramatic increase in airway hyperresponsiveness (AHR) to methacholine challenge, and greater airway cellular inflammation, compared to wild type (WT) mice. TS-exposed CSE KO mice that were subsequently infected with RSV exhibited more severe clinical disease, airway obstruction and AHR, enhanced viral replication and lung inflammation, compared to TS-exposed RSV-infected WT mice. TS-exposed RSV-infected CSE KO mice had also a significant increase in the number of neutrophils in bronchoalveolar lavage (BAL) fluid and increased levels of inflammatory cytokines and chemokines. CONCLUSION: This study demonstrates the critical contribution of the H(2)S-generating pathway to airway reactivity and disease following exposure to ETS alone or in combination with RSV infection.
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spelling pubmed-65948762019-10-15 CYSTATHIONINE γ-LYASE DEFICIENCY ENHANCES AIRWAY REACTIVITY AND VIRAL-INDUCED DISEASE IN MICE EXPOSED TO SIDE-STREAM TOBACCO SMOKE Ivanciuc, Teodora Sbrana, Elena Casola, Antonella Garofalo, Roberto P. Pediatr Res Article BACKGROUND: Environmental tobacco smoke (ETS) is a known risk factor for severe respiratory syncytial virus (RSV) infections, yet the mechanisms of ETS/RSV co-morbidity are largely unknown. Cystathionine γ-lyase regulates important physiological functions of the respiratory tract. METHODS: We used mice genetically deficient in the cystathionine γ-lyase enzyme (CSE), the major H(2)S-generating enzyme in the lung to determine the contribution of H(2)S to airway disease in response to side-stream tobacco smoke (TS), and to TS /RSV co-exposure. RESULTS: Following a two-week period of exposure to TS, CSE-deficient mice (KO) showed a dramatic increase in airway hyperresponsiveness (AHR) to methacholine challenge, and greater airway cellular inflammation, compared to wild type (WT) mice. TS-exposed CSE KO mice that were subsequently infected with RSV exhibited more severe clinical disease, airway obstruction and AHR, enhanced viral replication and lung inflammation, compared to TS-exposed RSV-infected WT mice. TS-exposed RSV-infected CSE KO mice had also a significant increase in the number of neutrophils in bronchoalveolar lavage (BAL) fluid and increased levels of inflammatory cytokines and chemokines. CONCLUSION: This study demonstrates the critical contribution of the H(2)S-generating pathway to airway reactivity and disease following exposure to ETS alone or in combination with RSV infection. 2019-04-15 2019-07 /pmc/articles/PMC6594876/ /pubmed/30986815 http://dx.doi.org/10.1038/s41390-019-0396-6 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Ivanciuc, Teodora
Sbrana, Elena
Casola, Antonella
Garofalo, Roberto P.
CYSTATHIONINE γ-LYASE DEFICIENCY ENHANCES AIRWAY REACTIVITY AND VIRAL-INDUCED DISEASE IN MICE EXPOSED TO SIDE-STREAM TOBACCO SMOKE
title CYSTATHIONINE γ-LYASE DEFICIENCY ENHANCES AIRWAY REACTIVITY AND VIRAL-INDUCED DISEASE IN MICE EXPOSED TO SIDE-STREAM TOBACCO SMOKE
title_full CYSTATHIONINE γ-LYASE DEFICIENCY ENHANCES AIRWAY REACTIVITY AND VIRAL-INDUCED DISEASE IN MICE EXPOSED TO SIDE-STREAM TOBACCO SMOKE
title_fullStr CYSTATHIONINE γ-LYASE DEFICIENCY ENHANCES AIRWAY REACTIVITY AND VIRAL-INDUCED DISEASE IN MICE EXPOSED TO SIDE-STREAM TOBACCO SMOKE
title_full_unstemmed CYSTATHIONINE γ-LYASE DEFICIENCY ENHANCES AIRWAY REACTIVITY AND VIRAL-INDUCED DISEASE IN MICE EXPOSED TO SIDE-STREAM TOBACCO SMOKE
title_short CYSTATHIONINE γ-LYASE DEFICIENCY ENHANCES AIRWAY REACTIVITY AND VIRAL-INDUCED DISEASE IN MICE EXPOSED TO SIDE-STREAM TOBACCO SMOKE
title_sort cystathionine γ-lyase deficiency enhances airway reactivity and viral-induced disease in mice exposed to side-stream tobacco smoke
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594876/
https://www.ncbi.nlm.nih.gov/pubmed/30986815
http://dx.doi.org/10.1038/s41390-019-0396-6
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