Preeclampsia-Related Inflammatory Cytokines Regulate Interleukin-6 Expression in Human Decidual Cells

Abstract

Preeclampsia, a common pregnancy disorder associated with an increase in systemic inflammation, is the leading cause of maternal and fetal morbidity and mortality throughout the world. It is associated with shallow extravillous trophoblast invasion of the decidua, leading to uteroplacental blood flow that is inadequate for the developing fetal-placental unit. In preeclamptic women, interleukin-6 (IL-6) levels in plasma, but not placenta, are elevated, prompting evaluation of the decidua as a potential source of this excess, circulating IL-6. The current study found significantly higher immunohistochemical staining for IL-6 in decidual cells from preeclamptic versus preterm, gestational age-matched control placentas. Proinflammatory cytokines associated with the genesis of preeclampsia (i.e., tumor necrosis factor-␣ and interleukin-1␤) enhanced IL-6 mRNA levels and increased secreted IL-6 levels in first trimester leukocytefree decidual cell incubations, as measured by real time quantitative RT-PCR , ELISA , and Western blotting. Therefore , decidual cell-derived IL-6 may contribute to excess circulating IL-6 levels that can promote both endothelial cell dysfunction (and subsequent vascular dysfunction) and the pathogenesis of preeclampsia whereas locally elevated IL-6 levels may contribute to an excess of decidual macrophages implicated in shallow extravillous trophoblast invasion of the decidua. Maternal-fetal interactions create a mild systemic inflammatory state exemplified by activation of both vascular endothelium and leukocytes that is most apparent in the third trimester of uncomplicated human pregnancies.

Regulation of Interleukin-6 Expression in Human Decidual Cells and Its Potential Role in Chorioamnionitis

“…Levels of IL-6 in the amniotic fluid of women with infection were found to enhance the production of uterine contraction-mediating prostaglandin E 2 when incubated with amnion or DCs, thereby suggesting a mechanism to account for CAM-associated PTD. 27 As in our evaluation of preeclamptic versus control decidual specimens, 10 the current study observed IL-6 immunostaining localized primarily in the cytoplasm of DCs that increased significantly in CAM versus control placental sections (HSCOREs, P Ͻ 0.05). In contrast, IL-6 HSCOREs were significantly lower in adjacent interstitial trophoblasts where the staining is primarily perimembranous and similar between patients and control subjects.…”

HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells

“…Much attention has been paid to the secretion of the proinflammatory cytokines described above as well as chemokines and VEGF by decidual NK cells and their possible roles in implantation that involves invasion of EVT into the decidua and in vascular remodeling of the uterine spiral arteries that insures an adequate blood supply to the developing fetus (14, 18-21,). IL-6 has received particular attention because of its possible role in preeclampsia (33). However, decidual macrophages that may make equal or more extensive contributions to these and other pregnancy-related phenomenon have been little studied.…”

Expression Profile of C19MC microRNAs in Placental Tissue in Pregnancy-Related Complications

“…Interleukin 6 Decidual cells from preeclamptic patients exhibit high IL6 production (Lockwood et al, 2008).…”