例如:"lncRNA", "apoptosis", "WRKY"

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

Pediatr Res. 2019 Jul;86(1):39-46. Epub 2019 Apr 15
Teodora Ivanciuc 1 , Elena Sbrana 2 , Antonella Casola 3 , Roberto P Garofalo 4
Teodora Ivanciuc 1 , Elena Sbrana 2 , Antonella Casola 3 , Roberto P Garofalo 4

[No authors listed]

Author information
  • 1 Department of Pediatrics, Division of Clinical and Experimental Immunology and Infectious Diseases (CEIID), University of Texas Medical Branch, Galveston, TX, USA.
  • 2 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
  • 3 Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA.
  • 4 Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA. rpgarofa@utmb.edu.

摘要


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 H2S-generating enzyme in the lung to determine the contribution of H2S 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 H2S-generating pathway to airway reactivity and disease following exposure to ETS alone or in combination with RSV infection.