title: Effects of interleukin-6 on extravillous trophoblast invasion in early human pregnancy.
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-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.
authors.affiliation: Reproductive and Vascular Biology Group,  Institute of Cellular Medicine, Newcastle University, 3rd Floor, William Leech Building, Newcastle-upon-Tyne NE2 4HH,  UK.
authors.forename: Hedele
authors.initials: H
authors.lastname: Champion
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Innes
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Robson
authors.forename: Gendie E
authors.initials: GE
authors.lastname: Lash
authors.forename: Judith N
authors.initials: JN
authors.lastname: Bulmer
mesh_terms: D019002:CD56 Antigen / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000378:metabolism; D002824:Chorionic Villi; D050822:Cytokine Receptor gp130 / Q000096:biosynthesis / Q000378:metabolism; D003656:Decidua / Q000378:metabolism; D010064:Embryo Implantation / Q000502:physiology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism; D015260:Neprilysin / Q000096:biosynthesis; D010766:Phosphorylation; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000502:physiology*; D014599:Uterus / Q000166:cytology
chemical_list: C483024:CCL5 protein, human; D019002:CD56 Antigen; D018946:Chemokine CCL5; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D015260:Neprilysin