title: Evidence for participation of uterine natural killer cells in the mechanisms responsible for spontaneous preterm labor and delivery.
abstract: OBJECTIVE
  The purpose of this study was to determine in a mouse model whether uterine natural killer (uNK) cell cytotoxic activation induces infection/inflammation-associated preterm labor and delivery.
  
  
  METHODS
  Wild type or interleukin (IL)-10(-/-) mice were injected intraperitoneally with lipopolysaccharide on gestational day 14. Mice were either killed for collection of uteroplacental tissue, spleen, and serum or allowed to deliver. Uteroplacental tissue was used for histology and characterization of uNK cells.
  
  
  RESULTS
  Low-dose lipopolysaccharide treatment triggered preterm labor and delivery in IL-10(-/-), but not wild type mice, in a manner independent of progesterone levels. Preterm labor and delivery in IL-10(-/-) mice was associated with an increased number and placental infiltration of cytotoxic uNK cells and placental cell death. Depletion of NK cells or tumor necrosis factor (TNF)-alpha neutralization in these mice restored term delivery. Furthermore, TNF-alpha neutralization prevented uNK cell infiltration and placental cell apoptosis.
  
  
  CONCLUSIONS
  The uNK cell-TNF-alpha-IL-10 axis plays an important role in the genesis of infection/inflammation-induced preterm labor/delivery.
authors.affiliation: Department of Pediatrics, Women and Infants Hospital of Rhode Island-Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Murphy
authors.forename: Nazeeh N
authors.initials: NN
authors.lastname: Hanna
authors.forename: Loren D
authors.initials: LD
authors.lastname: Fast
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Shaw
authors.forename: Göran
authors.initials: G
authors.lastname: Berg
authors.forename: James F
authors.initials: JF
authors.lastname: Padbury
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Surendra
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D005260:Female; D005865:Gestational Age; D007249:Inflammation / Q000150:complications / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008817:Mice, Mutant Strains; D007752:Obstetric Labor, Premature / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D010920:Placenta / Q000166:cytology / Q000276:immunology*; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014599:Uterus / Q000166:cytology / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10