Interleukin-1 family cytokines and their regulatory proteins in normal pregnancy and pre-eclampsia
Corresponding Author
J. H. Southcombe
Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU UK
Correspondence: J. H. Southcombe, Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK E-mail: [email protected]Search for more papers by this authorC. W. G. Redman
Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU UK
Search for more papers by this authorI. L. Sargent
Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU UK
Search for more papers by this authorI. Granne
Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU UK
Search for more papers by this authorCorresponding Author
J. H. Southcombe
Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU UK
Correspondence: J. H. Southcombe, Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK E-mail: [email protected]Search for more papers by this authorC. W. G. Redman
Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU UK
Search for more papers by this authorI. L. Sargent
Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU UK
Search for more papers by this authorI. Granne
Nuffield Department of Obstetrics and Gynaecology, Level 3 Women's Centre, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU UK
Search for more papers by this authorSummary
Maternal systemic inflammation is a feature of pre-eclampsia, a condition in pregnancy characterized by hypertension and proteinuria. Pre-eclampsia is caused by the placenta; many placental factors contribute to the syndrome's progression, and proinflammatory cytokines have been identified previously as one such mediator. The interleukin (IL)-1 family of cytokines are key regulators of the inflammatory network, and two naturally occurring regulatory molecules for IL-1 family cytokines, IL-1RA and sST2, have been found previously to be elevated in maternal blood from women with pre-eclampsia. Here we investigate more recently identified IL-1 family cytokines and regulatory molecules, IL-1RAcP, IL-37, IL-18BP, IL-36α/β/γ/Ra and IL-38 in pre-eclampsia. Pregnant women have more circulating IL-18BP and IL-36Ra than non-pregnant women, and sIL-1RAcP is elevated from women with pre-eclampsia compared to normal pregnancies. The placenta expresses all the molecules, and IL-37 and IL-18BP are up-regulated significantly in pre-eclampsia placentas compared to those from normal pregnancies. Together, these changes contribute to the required inhibition of maternal systemic cytotoxic immunity in normal pregnancy; however, in pre-eclampsia the same profile is not seen. Interestingly, the increased circulating levels of sIL-1RAcP and increased placental IL-18BP and IL-37, the latter of which we show to be induced by hypoxic damage to the placenta, are all factors which are anti-inflammatory. While the placenta is often held responsible for the damage and clinical symptoms of pre-eclampsia by the research community, here we show that the pre-eclampsia placenta is also trying to prevent inflammatory damage to the mother.
Supporting Information
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Fig. S1. Trophoblast cell lines express interleukin (IL)-1 family cytokines. Cell lysates from JEG-3, BeWo, SGHPL-5, AC1M59 and JAR cells were subjected to SDS-PAGE and Western blotting to detect sIL-1RAcP, IL-37, IL-18BP, IL-36α, IL-36β, IL-36γ, IL-36Ra, IL-38 and β-actin. |
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