Effects of interleukin-6 on extravillous trophoblast invasion in early human pregnancy
Date
2012
Authors
Champion, Hedele
Innes, Barbara
Robson, Stephen
Lash, Gendie
Bulmer, Judith
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Publisher
Oxford University Press
Abstract
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-6Ra 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-6Ra and gp130 were immunolocalized to EVT in placental bed
biopsies from 8 to 20 weeks gestation and IL-6Ra 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 Matrigelw 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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Keywords
trophoblast invasion, pregnancy, EVT, IL-6
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Source
Molecular Human Reproduction
Type
Journal article
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Restricted until
2099-12-31
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