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The role of interleukin-33 and its receptor ST2 in human pregnancy
  1. L A McKenna,
  2. F Jordan,
  3. E A Brown,
  4. S S Huda,
  5. V A Mackay,
  6. A M Miller,
  7. D J Freeman
  1. University of Glasgow, Glasgow, UK

Abstract

Introduction Placental cytokine expression differs between normal and complicated pregnancy (Williams et al, 2009). Interleukin-33 (IL-33) and its receptor ST2 are involved in lipid delivery in maternal adipose tissue. Our study hypothesised that IL-33 is an important pregnancy cytokine which influences early placental development and/or regulates fetal lipid supply.

Methods Maternal plasma, adipose tissue and placentas were sampled at caesarean section. Non-pregnant plasma was also analysed. IL-33 and ST2 messenger RNA (mRNA) expression was quantified by real-time PCR. IL-33 and ST2 protein was localised in healthy and complicated placentas by immunohistochemistry and plasma soluble ST2 (sST2) measured by ELISA.

Results Third trimester pregnant women had significantly higher plasma sST2 than non-pregnant women (p<0.001). Placental IL-33 and ST2 expression increases across gestation. In early pregnancy, IL-33 and ST2 are localised to syncytiotrophoblasts and later to the syncytium. Placental ST2 expression correlated with plasma sST2 levels in healthy pregnancy (r=0.36; p=0.02). IL-33 mRNA expression was 62% lower in IUGR placentas (p=0.003) and ST2 mRNA expression was 207% higher in pre-eclamptic placentas (p=0.002). In pre-eclamptic pregnancies, visceral adipose tissue ST2 expression was also 80% higher (p=0.02). In complicated pregnancy, IL-33 and ST2 staining appeared generally reduced.

Conclusions The IL-33/ST2 signalling pathway plays a role healthy pregnancy. The placenta is responsible for increased circulating sST2 in pregnancy. In IUGR, placental IL-33 is down-regulated, which may reduce circulating maternal triglycerides. In pre-eclampsia, placental ST2 expression increases and may promote increased lipolytic activity. Third trimester plasma sST2 levels did not differ between healthy and complicated pregnancy, indicating ST2 retention for IL-33 signalling.

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