Format

Send to

Choose Destination
PLoS One. 2019 Feb 28;14(2):e0212866. doi: 10.1371/journal.pone.0212866. eCollection 2019.

Dynamic changes in lung responses after single and repeated exposures to cigarette smoke in mice.

Author information

1
Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, United States of America.
2
Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC, United States of America.
3
Pathobiology and Translational Science Graduate Program, University of North Carolina, Chapel Hill, NC, United States of America.
4
Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina, Chapel Hill, NC, United States of America.
5
Department of Medicine, University of North Carolina, Chapel Hill, NC, United States of America.
6
Department of Genetics, University of North Carolina, Chapel Hill, NC, United States of America.
7
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States of America.

Abstract

Cigarette smoke is well recognized to cause injury to the airways and the alveolar walls over time. This injury usually requires many years of exposure, suggesting that the lungs may rapidly develop responses that initially protect it from this repetitive injury. Our studies tested the hypotheses that smoke induces an inflammatory response and changes in mRNA profiles that are dependent on sex and the health status of the lung, and that the response of the lungs to smoke differs after 1 day compared to 5 days of exposure. Male and female wildtype (WT) and Scnn1b-transgenic (βENaC) mice, which have chronic bronchitis and emphysematous changes due to dehydrated mucus, were exposed to cigarette smoke or sham air conditions for 1 or 5 days. The inflammatory response and gene expression profiles were analyzed in lung tissue. Overall, the inflammatory response to cigarette smoke was mild, and changes in mediators were more numerous after 1 than 5 days. βENaC mice had more airspace leukocytes than WT mice, and smoke exposure resulted in additional significant alterations. Many genes and gene sets responded similarly at 1 and 5 days: genes involved in oxidative stress responses were upregulated while immune response genes were downregulated. However, certain genes and biological processes were regulated differently after 1 compared to 5 days. Extracellular matrix biology genes and gene sets were upregulated after 1 day but downregulated by 5 days of smoke compared to sham exposure. There was no difference in the transcriptional response to smoke between WT and βENaC mice or between male and female mice at either 1 or 5 days. Taken together, these studies suggest that the lungs rapidly alter gene expression after only one exposure to cigarette smoke, with few additional changes after four additional days of repeated exposure. These changes may contribute to preventing lung damage.

Conflict of interest statement

The authors have declared that no competing interests exist.

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center