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This Article Full Text Full Text (PDF) All Versions of this Article: 296/3/L527    most recent 90506.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Li, T. Articles by Folkesson, H. G. Search for Related Content PubMed PubMed Citation Articles by Li, T. Articles by Folkesson, H. G.

IL-1β-induced cortisol stimulates lung fluid absorption in fetal guinea pigs via SGK-mediated Nedd4-2 inhibition

Department of Integrative Medical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, Ohio

Submitted 23 September 2008 ; accepted in final form 5 January 2009

We tested the hypothesis that interleukin (IL)-1β-induced cortisol synthesis stimulates distal lung fluid absorption in fetal guinea pigs via induction of serum- and glucocorticoid-regulated kinase (SGK) and inhibition of neural precursor cell expressed, developmentally downregulated protein 4-2 (Nedd4-2). IL-1β was subcutaneously administered daily to timed-pregnant guinea pigs over 3 days. Fetuses were obtained by abdominal hysterotomy at gestation day (GD)61 and GD68 and instilled with an isosmolar 5% albumin solution into the lungs. Distal lung fluid movement was measured over 1 h from the change in distal air space protein concentration. Fetal lungs were secreting lung fluid at GD61 while absorbing lung fluid at GD68. Distal lung fluid absorption was induced at GD61 by IL-1β but unaffected at GD68. Plasma cortisol concentrations were increased by IL-1β at GD61 and endogenously at GD68. Distal lung fluid absorption was measured and correlated to SGK and Nedd4-2 expression and to -epithelial Na channel (ENaC) expression. SGK was increased by IL-1β and late during gestation (GD68), while Nedd4-2 was decreased by IL-1β and late during gestation. -ENaC was induced by IL-1β at GD61 and increased late during gestation. Thus our study suggests that cortisol-stimulated fetal lung fluid absorption is mediated by increased ENaC expression and may be governed by the SGK/Nedd4-2 pathway. These observations may explain why babies delivered preterm after intrauterine inflammation have a reduced risk of developing severe respiratory distress.

alveolar epithelium; epithelial Na channels; lung development; sodium uptake