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

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....

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Bibliographic Details
Published in:Placenta (Eastbourne) Vol. 31; no. 7; pp. 595 - 601
Main Authors: De Oliveira, L.G., Lash, G.E., Murray-Dunning, C., Bulmer, J.N., Innes, B.A., Searle, R.F., Sass, N., Robson, S.C.
Format: Journal Article
Language:English
Published: Kidlington Elsevier Ltd 01.07.2010
Elsevier
Subjects:
Biological and medical sciences
CD8-Positive T-Lymphocytes - immunology
Cell Movement - physiology
Embryology: invertebrates and vertebrates. Teratology
Extravillous trophoblast
Female
Fundamental and applied biological sciences. Psychology
Humans
Interleukin 8
Interleukin-8 - immunology
Interleukin-8 - physiology
Internal Medicine
Invasion
Killer Cells, Natural - immunology
Matrix Metalloproteinase 2 - secretion
Obstetrics and Gynecology
Pregnancy - immunology
Pregnancy Trimester, First - immunology
Proteases
Receptors, Interleukin-8A - metabolism
Receptors, Interleukin-8B - metabolism
Trophoblasts - immunology
Trophoblasts - physiology
Uterine natural killer cells
Uterus - immunology
Extravillous trophoblast
Uterine natural killer cells
Proteases
Invasion
Interleukin 8
Natural killer cell
Trophoblaste
Vertebrata
Regulation(control)
Mammalia
Uterus
Fetal membrane
Female genital system
Cytokine
ISSN:0143-4004, 1532-3102, 1532-3102
Online Access:Get full text
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Summary: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. uNK cell stimulation of EVT invasion is associated with IL-8 levels. 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. 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. 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.
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ISSN:0143-4004
1532-3102
1532-3102
DOI:10.1016/j.placenta.2010.04.012