BACKGROUND: Caffeine is widely used to manage apnea of prematurity, and reduces the incidence of bronchopulmonary dysplasia (BPD). Deregulated transforming growth factor (TGF)-beta signaling underlies arrested postnatal lung maturation in BPD. It is unclear whether caffeine impacts TGF-beta signaling or postnatal lung development in affected lungs. METHODS: The impact of caffeine on TGF-beta signaling in primary mouse lung fibroblasts and alveolar epithelial type II cells was assessed in vitro. The effects of caffeine administration (25 mg/kg/d for the first 14 d of postnatal life) on aberrant lung development and TGF-beta signaling in vivo was assessed in a hyperoxia (85% O2)-based model of BPD in C57BL/6 mice. RESULTS: Caffeine downregulated expression of type I and type III TGF-beta receptors, and Smad2; and potentiated TGF-beta signaling in vitro. In vivo, caffeine administration normalized body mass under hyperoxic conditions, and normalized Smad2 phosphorylation detected in lung homogenates; however, caffeine administration neither improved nor worsened lung structure in hyperoxia-exposed mice, in which postnatal lung maturation was blunted. CONCLUSION: Caffeine modulated TGF-beta signaling in vitro and in vivo. Caffeine administration was well-tolerated by newborn mice, but did not influence the course of blunted postnatal lung maturation in a hyperoxia-based experimental mouse model of BPD.
- Rath, P.
- Nardiello, C.
- Surate Solaligue, D. E.
- Agius, R.
- Mizikova, I.
- Huhn, S.
- Mayer, K.
- Vadasz, I.
- Herold, S.
- Runkel, F.
- Seeger, W.
- Morty, R. E.
