Cargando…
Caffeine induces alveolar apoptosis in the hyperoxia-exposed developing mouse lung
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...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943688/ https://www.ncbi.nlm.nih.gov/pubmed/24321990 http://dx.doi.org/10.1038/pr.2013.233 |
Sumario: | 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-day period of hyperoxia and daily caffeine administration followed by a 14-day recovery period in room air. Lungs were collected at both time points for bronchoalveolar fluid (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 cell numbers, increased cell apoptosis, and decreased expression of A(2A) 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. |
---|