Interleukin-11 promotes migration, but not proliferation, of human trophoblast cells, implying a role in placentation.
Trophoblast growth and invasion of the uterine endometrium are critical events during placentation and are tightly regulated by factors produced within the trophoblast-endometrial microenvironment. Deficiencies in placentation can result in early miscarriage or preeclampsia and intrauterine growth restriction, leading to impaired fetal health. The latter has been linked to major adult health disorders. IL-11 is essential for blastocyst implantation in mice. In humans, IL-11 and its receptor IL-11 receptor alpha (IL-11Ralpha) are maximally expressed in the decidua and chorionic villi during early pregnancy; however, the role of IL-11 in trophoblast function is unknown. Therefore, we examined whether IL-11Ralpha is expressed in human first trimester implantation sites, and whether IL-11 influences proliferation and migration of a human extravillous trophoblast (EVT)-hybridoma cell line and primary EVT cells, used as models for EVT. Immunoreactive IL-11Ralpha localized to subpopulations of interstitial and endovascular EVT cells in vivo. In EVT cells in vitro, IL-11: 1) stimulated phosphorylation of signal transducer and activator of transcription-3; 2) was without effect on EVT cell proliferation; and 3) stimulated significant migration of EVT-hybridoma cells (no endogenous IL-11), whereas in primary EVT, blocking endogenous IL-11 inhibited EVT migration by 30-40%. These data demonstrate that IL-11 stimulates human EVT migration, but not proliferation, likely via signal transducer and activator of transcription-3, indicating an important role for IL-11 in placentation.
Paiva
Premila
P
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia. premila.paiva@princehenrys.org
Salamonsen
Lois A
LA
Manuelpillai
Ursula
U
Walker
Claire
C
Tapia
Alejandro
A
Wallace
Euan M
EM
Dimitriadis
Evdokia
E
D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D005260:Female; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D053703:Interleukin-11 Receptor alpha Subunit / Q000378:metabolism; D010929:Placentation / Q000187:drug effects*; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism
D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050822:Cytokine Receptor gp130; D011505:Protein-Tyrosine Kinases