Effects of interleukin-6 on extravillous trophoblast invasion in early human pregnancy

Invasion of uterine tissues by extravillous trophoblast cells (EVT) is essential for successful human pregnancy. EVT invasion is tightly regulated by a number of factors, including growth factors and cytokines, but the mechanisms that underlie their regulatory effect remain poorly understood. Interl...

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Bibliographic Details
Published in:Molecular human reproduction Vol. 18; no. 8; p. 391
Main Authors: Champion, Hedele, Innes, Barbara A, Robson, Stephen C, Lash, Gendie E, Bulmer, Judith N
Format: Journal Article
Language:English
Published: England 01.08.2012
Subjects:
CD56 Antigen - biosynthesis
CD8-Positive T-Lymphocytes - metabolism
Cell Line
Cell Movement - physiology
Chemokine CCL5 - biosynthesis
Chemokine CCL5 - metabolism
Chorionic Villi
Cytokine Receptor gp130 - biosynthesis
Cytokine Receptor gp130 - metabolism
Decidua - metabolism
Embryo Implantation - physiology
Female
Humans
Interleukin-6 - metabolism
Killer Cells, Natural - metabolism
Lipopolysaccharide Receptors - biosynthesis
Macrophages - metabolism
Neprilysin - biosynthesis
Phosphorylation
Pregnancy
Pregnancy Trimester, First
Receptors, Interleukin-6 - biosynthesis
Receptors, Interleukin-6 - metabolism
Signal Transduction
Stromal Cells - metabolism
Trophoblasts - cytology
Trophoblasts - physiology
Uterus - cytology
ISSN:1460-2407, 1460-2407
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Summary:Invasion of uterine tissues by extravillous trophoblast cells (EVT) is essential for successful human pregnancy. EVT invasion is tightly regulated by a number of factors, including growth factors and cytokines, but the mechanisms that underlie their regulatory effect remain poorly understood. Interleukin (IL)-6 has been suggested to play a role in controlling EVT invasion. We hypothesized that IL-6 produced by cells in uterine decidua would regulate EVT invasiveness via IL-6Rα and gp130 receptors expressed by trophoblast cells. The effect of IL-6 on EVT signalling and cytokine production was also studied. Supernatants from disaggregated 'total' decidual cells, CD8(+) T cells, CD10(+) decidual stromal cells, CD14 macrophages, CD56(+) uterine natural killer cells, cytotrophoblast and EVT cells contained large quantities of IL-6 protein at both 8-10 and 12-14 weeks gestational age. IL-6Rα and gp130 were immunolocalized to EVT in placental bed biopsies from 8 to 20 weeks gestation and IL-6Rα expression was confirmed by western blotting. IL-6 had no effect on the invasive potential of EVT from chorionic villi or the immortalized EVT cell line HTR-8/SVneo in a Matrigel(®) invasion assay. IL-6 stimulated phosphorylation of several cell signalling proteins in EVT (8-14 weeks' gestation), although significance was lost after correction for multiple comparisons. Incubation with IL-6 decreased secretion of regulated upon activation, normal T-cell expressed and secreted (RANTES) by EVT cells. In conclusion, although IL-6 did not affect trophoblast cell invasion, it stimulated EVT cellular cascades and inhibited secretion of RANTES involved in a number of cellular processes.
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ISSN:1460-2407
1460-2407
DOI:10.1093/molehr/gas010