Caffeine induces alveolar apoptosis in the hyperoxia-exposed developing mouse lung.

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.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Dayanim S,Lopez B,Maisonet TM,Grewal S,Londhe VA

doi

10.1038/pr.2013.233

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

395-402

issue

3

eissn

0031-3998

issn

1530-0447

pii

pr2013233

journal_volume

75

pub_type

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