Cigarette smoke exposure reduces leukemia inhibitory factor levels during respiratory syncytial viral infection

Justin Poon, Michael Campos, Robert F. Foronjy, Sridesh Nath, Gayatri Gupta, Christopher Railwah, Abdoulayej Dabo, Nathalie Baumlin, Matthias Salathe, Patrick Geraghty

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Background: Viral infections are considered a major driving factor of chronic obstructive pulmonary disease (COPD) exacerbations and thus contribute to disease morbidity and mortality. Respiratory syncytial virus (RSV) is a frequently detected pathogen in the respiratory tract of COPD patients during an exacerbation. We previously demonstrated in a murine model that leukemia inhibitory factor (LIF) expression was increased in the lungs during RSV infection. Subduing LIF signaling in this model enhanced lung injury and airway hypersensitivity. In this study, we investigated lung LIF levels in COPD patient samples to determine the impact of disease status and cigarette smoke exposure on LIF expression. Materials and methods: Bronchoalveolar lavage fluid (BALF) was obtained from healthy never smokers, smokers, and COPD patients, by written informed consent. Human bronchial epithelial (HBE) cells were isolated from healthy never smokers and COPD patients, grown at the air–liquid interface and infected with RSV or stimulated with polyinosinic:polycytidylic acid (poly (i:c)). Mice were exposed to cigarette smoke daily for 6 months and were subsequently infected with RSV. LIF expression was profiled in all samples. Results: In human BALF, LIF protein was significantly reduced in both smokers and COPD patients compared to healthy never smokers. HBE cells isolated from COPD patients produced less LIF compared to never smokers during RSV infection or poly (i:c) stimulation. Animals exposed to cigarette smoke had reduced lung levels of LIF and its corresponding receptor, LIFR. Smoke-exposed animals had reduced LIF expression during RSV infection. Two possible factors for reduced LIF levels were increased LIF mRNA instability in COPD epithelia and proteolytic degradation of LIF protein by serine proteases. Conclusions: Cigarette smoke is an important modulator for LIF expression in the lungs. Loss of LIF expression in COPD could contribute to a higher degree of lung injury during virus-associated exacerbations.

Original languageEnglish (US)
Pages (from-to)1305-1315
Number of pages11
JournalInternational Journal of COPD
Volume14
DOIs
StatePublished - 2019

Keywords

  • Chronic obstructive pulmonary disease
  • Cigarette smoke
  • Leukemia inhibitory factor
  • Respiratory syncytial virus

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Health Policy
  • Public Health, Environmental and Occupational Health

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  • Cite this

    Poon, J., Campos, M., Foronjy, R. F., Nath, S., Gupta, G., Railwah, C., Dabo, A., Baumlin, N., Salathe, M., & Geraghty, P. (2019). Cigarette smoke exposure reduces leukemia inhibitory factor levels during respiratory syncytial viral infection. International Journal of COPD, 14, 1305-1315. https://doi.org/10.2147/COPD.S196658