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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Vydané v:	Placenta (Eastbourne) Ročník 31; číslo 7; s. 595 - 601
Hlavní autori:	De Oliveira, L.G., Lash, G.E., Murray-Dunning, C., Bulmer, J.N., Innes, B.A., Searle, R.F., Sass, N., Robson, S.C.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Kidlington Elsevier Ltd 01.07.2010 Elsevier
Predmet:	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
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Abstract	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.
AbstractList	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.BACKGROUNDExtravillous 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.HYPOTHESISuNK 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.METHODSCD8+, 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.RESULTSHigh 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.CONCLUSIONuNK 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. 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. 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. 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.
Author	Bulmer, J.N. Innes, B.A. Searle, R.F. Sass, N. Murray-Dunning, C. De Oliveira, L.G. Lash, G.E. Robson, S.C.
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Keywords	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
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Snippet	Extravillous trophoblast cell (EVT) invasion of maternal tissues is critical for successful pregnancy. Decidual factors, including uterine natural killer (uNK)... Abstract Background Extravillous trophoblast cell (EVT) invasion of maternal tissues is critical for successful pregnancy. Decidual factors, including uterine...
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StartPage	595
SubjectTerms	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
Title	Role of Interleukin 8 in Uterine Natural Killer Cell Regulation of Extravillous Trophoblast Cell Invasion
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Volume	31
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