Transcription factors NF-kappaB and C/EBPdelta and IL-1-induced expression of surfactant protein A in lung explants during the perinatal period.
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.
Seppänen
Outi
O
Department of Pediatrics and Biocenter Oulu, University of Oulu, Oulu, Finland.
Glumoff
Virpi
V
Paananen
Reija
R
Rounioja
Samuli
S
Hallman
Mikko
M
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016384:Consensus Sequence; D005333:Fetus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology*; D008168:Lung / Q000196:embryology* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D009924:Organ Culture Techniques; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; D007375:Interleukin-1; D016328:NF-kappa B; D009687:Nuclear Proteins; D037662:Pulmonary Surfactant-Associated Protein A; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta