Release of cytokines and apoptosis in fetal rat Type II pneumocytes exposed to hyperoxia and nitric oxide: modulatory effects of dexamethasone and pentoxifylline.
The response of the fetal rat Type II pneumocyte (FTIIP), the stem cell of the alveolar epithelium, to hyperoxia would be helpful to understand the effects of oxygen-induced injury to the immature lung. In such a scenario, the presence of nitric oxide (NO) may have a protective or detrimental effect. Our goals were to evaluate the release of cytokines and apoptotic cell death in freshly isolated FTIIP (19-day) in the presence of 95% O(2) and/or NO. The effects of dexamethasone and pentoxifylline on the FTIIP cytokine response were also studied. There was no significant difference in the levels of IL-1beta and IL-10 from FTIIP, in room air, hyperoxia and/or NO at 2, 6 and 24 h. However, IL-6 release was significantly higher, when measured over time, after 2, 6 and 24 h of exposure to hyperoxia and NO. Dexamethasone in the presence of hyperoxia and/or NO increased the release of IL-10 at 24 h. There was increased apoptosis in FTIIP exposed to hyperoxia alone and in combination with NO; this was significantly attenuated in the presence of dexamethasone and pentoxifylline. We speculate that the cytoprotective effects of dexamethasone in the immature lung may, in part, be mediated via IL-10.
Gavino
R
R
Department of Pediatrics, Albert Einstein Medical Center, Philadelphia, PA, USA.
Johnson
L
L
Bhandari
V
V
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016207:Cytokines / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D018496:Hyperoxia / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010431:Pentoxifylline / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D016166:Free Radical Scavengers; D005938:Glucocorticoids; D009569:Nitric Oxide; D003907:Dexamethasone; D010431:Pentoxifylline