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Role of Interleukin 8 in Uterine Natural Killer Cell Regulation of Extravillous Trophoblast Cell Invasion

Lookup NU author(s): Dr Gendie Lash, Dr Judith Bulmer, Barbara Innes, Dr Roger Searle, Professor Stephen Robson

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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. Hypothesis: 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. Conclusion: 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. (C) 2010 Elsevier Ltd. All rights reserved.


Publication metadata

Author(s): De Oliveira LG, Lash GE, Murray-Dunning C, Bulmer JN, Innes BA, Searle RF, Sass N, Robson SC

Publication type: Article

Publication status: Published

Journal: Placenta

Year: 2010

Volume: 31

Issue: 7

Pages: 595-601

Print publication date: 18/05/2010

ISSN (print): 0143-4004

ISSN (electronic): 1532-3102

Publisher: Elsevier Ltd

URL: http://dx.doi.org/10.1016/j.placenta.2010.04.012

DOI: 10.1016/j.placenta.2010.04.012


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