Surfactant protein D modulates levels of IL-10 and TNF-α in intrauterine compartments during lipopolysaccharide-induced preterm birth.
Prematurity is the main cause of perinatal mortality and morbidity, and preterm birth is often associated with intrauterine inflammation. Surfactant protein D (SP-D) functions in lung homeostasis and has multiple roles in innate immunity. It is present in amniotic fluid and in gestational tissues. We propose that SP-D may regulate intrauterine inflammatory responses related to preterm labor. Our aim was to investigate the role of SP-D in lipopolysaccharide-induced preterm birth in mice that overexpress rat SP-D (rSP-D) under the human SP-C promoter. SP-D protein in amniotic fluid and in gestational tissues was detected by western analysis. TNF-α, IL-10, and IL-6 concentrations in serum and amniotic fluid and mRNA levels in gestational tissues were quantified using cytometric bead array and ribonuclease protection assay, respectively. Increased levels of SP-D protein were detected in the amniotic fluid and gestational tissues of rSP-D mice. Lipopolysaccharide given at 17 days post-coitum to rSP-D dams led to preterm birth of live-born offspring within 18 h. Preterm birth of live-born pups was induced with a lower dose of lipopolysaccharide compared to wild-type mice. In rSP-D mice, the lipopolysaccharide-induced levels of TNF-α and IL-10 in amniotic fluid and fetal serum and the expression of IL-10 in placenta and fetal membranes were significantly different from wild-type mice. We conclude that SP-D in fetal and gestational tissues modulates the levels of intrauterine inflammatory mediators involved in preterm birth and may contribute to inflammatory processes related to spontaneous preterm labor.
Institute of Clinical Medicine, Department of Pediatrics, University of Oulu, FI-90014 Oulu, Finland. annamari.salminen@oulu.fi
Annamari
A
Salminen
Reetta
R
Vuolteenaho
Reija
R
Paananen
Marja
M
Ojaniemi
Mikko
M
Hallman
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D005321:Extraembryonic Membranes / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism*; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D047928:Premature Birth / Q000097:blood / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism*; D051381:Rats; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism*
D008070:Lipopolysaccharides; D037663:Pulmonary Surfactant-Associated Protein D; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10