Abstract
Background:
Caffeine is a nonspecific adenosine receptor antagonist used in premature neonates to treat apnea of prematurity. While its use may reduce the incidence of bronchopulmonary dysplasia (BPD), the precise mechanisms remain unknown. Evidence of increased adenosine levels are noted in chronic lung diseases including tracheal aspirates of infants with BPD. Utilizing a well-characterized newborn mouse model of alveolar hypoplasia, we hypothesized that hyperoxia-induced alveolar inflammation and hypoplasia is associated with alterations in the adenosine signaling pathway.
Methods:
Newborn murine pups were exposed to a 14-d period of hyperoxia and daily caffeine administration followed by a 14-d recovery period in room air. Lungs were collected at both time points for bronchoalveolar lavage (BAL) analysis as well as histopathology and mRNA and protein expression.
Results:
Caffeine treatment increased inflammation and worsened alveolar hypoplasia in hyperoxia-exposed newborn mice. These changes were associated with decreased alveolar type II (ATII) cell numbers, increased cell apoptosis, and decreased expression of A2A receptors. Following discontinuation of caffeine and hyperoxia, lung histology returned to baseline levels comparable to hyperoxia exposure alone.
Conclusion:
Results of this study suggest a potentially adverse role of caffeine on alveolar development in a murine model of hyperoxia-induced alveolar hypoplasia.
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Acknowledgements
We thank Bo-Chul Shin and the Devaskar lab, Neonatal Research Center, University of California, Los Angeles, for use and assistance with the immunofluorescence microscope. We also thank John Belperio in the Division of Pulmonary and Critical Care at University of California, Los Angeles for providing the hyperoxia apparatus.
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Dayanim, S., Lopez, B., Maisonet, T. et al. Caffeine induces alveolar apoptosis in the hyperoxia-exposed developing mouse lung. Pediatr Res 75, 395–402 (2014). https://doi.org/10.1038/pr.2013.233
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DOI: https://doi.org/10.1038/pr.2013.233
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