Cystathionine γ-lyase deficiency enhances airway reactivity and viral-induced disease in mice exposed to side-stream tobacco smoke

Teodora Ivanciuc, Elena Sbrana, Antonella Casola, Roberto Garofalo

Research output: Contribution to journalArticle

Abstract

Background: Environmental tobacco smoke (ETS) is a known risk factor for severe respiratory syncytial virus (RSV) infections, yet the mechanisms of ETS/RSV comorbidity 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 2-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 with wild-type (WT) mice. TS-exposed CSE KO mice that were subsequently infected with RSV exhibited a more severe clinical disease, airway obstruction and AHR, enhanced viral replication, and lung inflammation, compared with 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 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.

Original languageEnglish (US)
JournalPediatric Research
DOIs
StatePublished - Jan 1 2019

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Cystathionine
Lyases
Virus Diseases
Smoke
Tobacco
Respiratory Syncytial Viruses
Enzymes
Respiratory Syncytial Virus Infections
Methacholine Chloride
Environmental Exposure
Bronchoalveolar Lavage Fluid
Airway Obstruction
Chemokines
Respiratory System
Comorbidity
Pneumonia
Neutrophils
Cytokines
Inflammation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

@article{c5f1afb338354112a12249ac9e4ae924,
title = "Cystathionine γ-lyase deficiency enhances airway reactivity and viral-induced disease in mice exposed to side-stream tobacco smoke",
abstract = "Background: Environmental tobacco smoke (ETS) is a known risk factor for severe respiratory syncytial virus (RSV) infections, yet the mechanisms of ETS/RSV comorbidity 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 2-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 with wild-type (WT) mice. TS-exposed CSE KO mice that were subsequently infected with RSV exhibited a more severe clinical disease, airway obstruction and AHR, enhanced viral replication, and lung inflammation, compared with 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 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.",
author = "Teodora Ivanciuc and Elena Sbrana and Antonella Casola and Roberto Garofalo",
year = "2019",
month = "1",
day = "1",
doi = "10.1038/s41390-019-0396-6",
language = "English (US)",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",

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T1 - Cystathionine γ-lyase deficiency enhances airway reactivity and viral-induced disease in mice exposed to side-stream tobacco smoke

AU - Ivanciuc, Teodora

AU - Sbrana, Elena

AU - Casola, Antonella

AU - Garofalo, Roberto

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Environmental tobacco smoke (ETS) is a known risk factor for severe respiratory syncytial virus (RSV) infections, yet the mechanisms of ETS/RSV comorbidity 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 2-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 with wild-type (WT) mice. TS-exposed CSE KO mice that were subsequently infected with RSV exhibited a more severe clinical disease, airway obstruction and AHR, enhanced viral replication, and lung inflammation, compared with 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 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.

AB - Background: Environmental tobacco smoke (ETS) is a known risk factor for severe respiratory syncytial virus (RSV) infections, yet the mechanisms of ETS/RSV comorbidity 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 2-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 with wild-type (WT) mice. TS-exposed CSE KO mice that were subsequently infected with RSV exhibited a more severe clinical disease, airway obstruction and AHR, enhanced viral replication, and lung inflammation, compared with 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 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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