title: Role of interleukin 8 in uterine natural killer cell regulation of extravillous trophoblast cell invasion.
abstract: BACKGROUND
  Extravillous trophoblast cell (EVT) invasion of maternal tissues is critical for successful pregnancy. Decidual factors, including uterine natural killer (uNK) and T cell derived cytokines play a role in regulating this process. Interleukin (IL) 8 has been implicated as a regulator of EVT invasion.
  
  
  OBJECTIVE
  uNK cell stimulation of EVT invasion is associated with IL-8 levels.
  
  
  METHODS
  CD8+, total decidual and CD56(+) uNK cells (8-10 and 12-14 weeks gestational age) were cultured. IL-8 mRNA and protein levels were determined. IL-8 receptors (IL-8RA and IL-8RB) were localised in first trimester placental bed biopsies. The effect of IL-8 +/- IL-8 neutralising antibodies and CD8+ T cell or uNK cell supernatants +/- IL-8 neutralising antibodies on EVT invasion was assessed. EVT secreted levels of MMP-2, MMP-9, uPA, PAI-1 and PAI-2 were assessed by substrate zymography or Western Blot.
  
  
  RESULTS
  High levels of IL-8 protein and mRNA were detected in all samples. IL-8RA and IL-8RB were expressed by EVT. Exogenous IL-8 stimulated EVT invasion in a paracrine manner. uNK cell supernatants, but not CD8+ cell supernatants, stimulated EVT invasion. IL-8 neutralising antibody partially abrogated this uNK cell stimulated invasion. IL-8 increased levels of secreted MMP-2, but did not alter any of the other proteases or protease inhibitors tested.
  
  
  CONCLUSIONS
  uNK cell stimulation of EVT invasion is partially mediated by IL-8. Unstimulated CD8+ T cells do not alter EVT invasion despite secreting similar levels of IL-8 as uNK cells.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: L G
authors.initials: LG
authors.lastname: De Oliveira
authors.forename: G E
authors.initials: GE
authors.lastname: Lash
authors.forename: C
authors.initials: C
authors.lastname: Murray-Dunning
authors.forename: J N
authors.initials: JN
authors.lastname: Bulmer
authors.forename: B A
authors.initials: BA
authors.lastname: Innes
authors.forename: R F
authors.initials: RF
authors.lastname: Searle
authors.forename: N
authors.initials: N
authors.lastname: Sass
authors.forename: S C
authors.initials: SC
authors.lastname: Robson
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000502:physiology; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D011247:Pregnancy / Q000276:immunology*; D011261:Pregnancy Trimester, First / Q000276:immunology; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D014327:Trophoblasts / Q000276:immunology* / Q000502:physiology*; D014599:Uterus / Q000276:immunology*
chemical_list: D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D020778:Matrix Metalloproteinase 2