Interleukin-1 (IL-1) increases the expression of surfactant protein A (SP-A) in rabbit, lamb and human fetal lung. The upregulation disappears towards term. Among the transcription factors, IL-1 activates nuclear factor kappaB (NF-kappaB) and CCAAT/enhancer-binding protein delta (C/EBPdelta). NF-kappaB presumably has a role in IL-1-induced upregulation of SP-A. Also, C/EBPdelta may regulate SP-A expression. The aim was to study the role of these transcription factors in the induced effect of IL-1 on SP-A expression. Explants from fetal and neonatal rabbit lung were cultured in vitro followed by studies using immunohistochemistry, electrophoretic mobility shift assay and Northern analysis. We found gestation-dependent changes in IL-1-induced immunoreactivities of NF-kappaB and C/EBPdelta in the nuclei of alveolar cells. This increase in nuclear transcription factors correlated with IL-1-induced SP-A expression levels. As studied in the explants from fetal and newborn lung, the SP-A mRNA expression additionally associated with C/EBPdelta mRNA and with the binding of nuclear extracts from the lung explants to the C/EBP consensus probe. On the basis of the present and previous studies, we propose that NF-kappaB and C/EBPdelta have potential mediator roles in IL-1-induced upregulation of SP-A in immature lung.
Copyright (c) 2005 S. Karger AG, Basel.