| First Author | Ivanciuc T | Year | 2019 |
| Journal | Pediatr Res | Volume | 86 |
| Issue | 1 | Pages | 39-46 |
| PubMed ID | 30986815 | Mgi Jnum | J:295797 |
| Mgi Id | MGI:6454463 | Doi | 10.1038/s41390-019-0396-6 |
| Citation | Ivanciuc T, et al. (2019) Cystathionine gamma-lyase deficiency enhances airway reactivity and viral-induced disease in mice exposed to side-stream tobacco smoke. Pediatr Res 86(1):39-46 |
| abstractText | 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 gamma-lyase regulates important physiological functions of the respiratory tract. METHODS: We used mice genetically deficient in the cystathionine gamma-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. |
