107. INTERLEUKIN 11 AND LEUKEMIA INHIBITORY FACTOR REGULATE CYTOKINE NETWORKS IN HUMAN FIRST TRIMESTER PLACENTA
E. Dimitriadis A , P. Paiva A , U. Manuelpillai B , G. Weston C , K. Meehan A and J. Yap AA Prince Henry's Institute of Medical Research, Melbourne, VIC, Australia.
B Monash Institute of Medical Research, Monash University, VIC, Australia.
C Centre for Women’s Health Research and Dept. of Obstetric and Gynaecology, Monash, VIC, Australia.
Reproduction, Fertility and Development 21(9) 26-26 https://doi.org/10.1071/SRB09Abs107
Published: 26 August 2009
Abstract
Inadequate trophoblast invasion is thought to be involved in the pathogenesis of preeclampsia (PE). Shallow trophoblast invasion has been implicated to lead to placental hypoxia and a localised overproduction of pro-inflammatory cytokines. Interleukin (IL) 11 and leukemia inhibitory factor (LIF) are IL6-type cytokines produced at the maternal-fetal interphase and regulate human trophoblast migration/invasion, but their mechanisms of action are unknown. We aimed to determine the effect of hypoxia on human placental IL11/LIF secretion and the effect of IL11/LIF on placental cytokine secretion. As an in vitro model we cultured human first trimester placental villous explants (gestation weeks 7-9) in serum free conditions under either 2% (hypoxia) or 20% oxygen (normoxia) (N=8/gp) for 48h. Medium was assayed for IL11/LIF by ELISA. The effect of IL11/LIF (N=6/gp) on placental explant cytokine secretion (26 cytokines) was analysed using a quantitative multiplex immunoassay. Data was expressed as pg/mg wet weight and then as % change vs control (100%). IL11 secretion from explants was decreased by 76±5% (p<0.01) under hypoxia vs normoxia while LIF secretion did not differ significantly. Under normoxia the most highly abundant cytokines were IL6, IL8 and MCP-1 while moderate levels of G-CSF, CX3CL1, IP-10, and PGDF were present in conditioned medium. IL11 increased IL10 secretion while it decreased G-CSF, TNFa, IL1receptor antagonist (Ra), IL6 and PDGF secretion (p<0.05) vs control. Similarly LIF decreased G-CSF, TNFa, IL1Ra and additionally IL8 secretion (p<0.05) vs control. IL6 and VEGF secretion were increased (p<0.05) while MCP-1 was reduced (p<0.05) by hypoxia vs normoxia. This study identified for the first time that IL11 was reduced by hypoxia and identified a profile of cytokines secreted by placenta. IL11 and LIF regulated similar and unique anti-inflammatory cytokines in first trimester placenta. Whether placental IL11 or LIF is altered in women with PE remains to be elucidated however this study suggests mechanisms of action and confirms the importance of IL11/LIF in placentation.
