title: Interleukin 11 inhibits human trophoblast invasion indicating a likely role in the decidual restraint of trophoblast invasion during placentation.
abstract: Successful pregnancy depends on the precise regulation of extravillous trophoblast (EVT) invasion into the uterine decidua, primarily by decidua-derived factors. In humans, during early pregnancy interleukin 11 (IL11) is maximally expressed in the decidua, with its receptor, IL11 receptor alpha (IL11RA), also identified on invasive EVTs in vivo. Although a role for IL11 in EVT migration has been established, whether it also plays a role in regulating EVT invasion is unknown. We investigated whether IL11 influences human EVT invasion and the signaling pathways and underlying mechanisms that may be involved, using the HTR-8/SVneo immortalized EVT cell line and primary EVTs as models for EVTs. Interleukin 11 (100 ng/ml) significantly inhibited invasion of EVT cells by 40% to 60% (P < 0.001). This effect was abolished by inhibitors of signal transducer and activator of transcription 3 (STAT3) but not of mitogen-activated protein kinase (MAPK) pathways. Interleukin 11 (100 ng/ml) had no effect on matrix metallopeptidases 2 and 9 (MMP2 and MMP9), tissue inhibitors of MMP (TIMP1, TIMP2, and TIMP3), plasminogen activator urokinase (PLAU), plasminogen activator urokinase receptor (PLAUR), and serpin peptidase inhibitors 1 and 2 (SERPINE1 and SERPINE2) in EVT-conditioned media and/or cell lysates. Interleukin 11 (100 ng/ml) also did not regulate EVT cell adhesion or integrin expression. These data demonstrate that IL11 inhibits human EVT invasion via STAT3, indicating a likely role for IL11 in the decidual restraint of EVT invasion during normal pregnancy.
authors.affiliation: Prince Henry's Institute of Medical Research, Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria 3800, Australia. premila.paiva@princehenrys.org
authors.forename: Premila
authors.initials: P
authors.lastname: Paiva
authors.forename: Lois A
authors.initials: LA
authors.lastname: Salamonsen
authors.forename: Ursula
authors.initials: U
authors.lastname: Manuelpillai
authors.forename: Evdokia
authors.initials: E
authors.lastname: Dimitriadis
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D003656:Decidua / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D053703:Interleukin-11 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D010929:Placentation / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D011247:Pregnancy; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: C508611:IL11 protein, human; C508428:IL11RA protein, human; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases