Regulation of surfactant proteins by LPS and proinflammatory cytokines in fetal and newborn lung.
Intra-amniotic lipopolysaccharide (LPS) and cytokines may decrease respiratory distress syndrome (RDS) and increase chronic lung disease in the newborn. The aim was to identify the primary inflammatory mediators regulating the expression of surfactant proteins (SP) in explants from immature (22-day-old fetus) and mature (30-day term fetus and 2-day-old newborn) rabbits. In immature lung, interleukin (IL)-1alpha and IL-1beta upregulated the expression of SP-A and SP-B. These effects of IL-1 were diminished, and SP-C mRNA was suppressed additively in the presence of tumor necrosis factor (TNF)-alpha and either LPS or interferon (IFN)-gamma. LPS, TNF-alpha, or IFN-gamma had no effect alone. In explants from the term fetus and the newborn, LPS, IL-1alpha, and TNF-alpha additively suppressed the SPs. LPS acutely induced IL-1alpha in alveolar macrophages in mature lung but not in the immature lung. IFN-gamma that generally has low expression in intrauterine infection decreased the age dependence of the other agonists' effects on SPs. The present study serves to explain the variation of the pulmonary outcome after an inflammatory insult. We propose that IL-1 from extrapulmonary sources induces the SPs in premature lung and is responsible for the decreased risk of RDS in intra-amniotic infection.
Väyrynen
Outi
O
Department of Pediatrics, Biocenter Oulu, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland. ovayryne@paju.oulu.fi
Glumoff
Virpi
V
Hallman
Mikko
M
D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D000970:Antineoplastic Agents / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism; D009924:Organ Culture Techniques; D011247:Pregnancy; D011510:Proteolipids / Q000235:genetics* / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D012127:Respiratory Distress Syndrome, Newborn / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000970:Antineoplastic Agents; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma