Preeclampsia-related inflammatory cytokines regulate interleukin-6 expression in human decidual cells.
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. Pro-inflammatory cytokines associated with the genesis of preeclampsia (i.e., tumor necrosis factor-alpha and interleukin-1beta) enhanced IL-6 mRNA levels and increased secreted IL-6 levels in first trimester leukocyte-free 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.
Lockwood
Charles J
CJ
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
Yen
Chih-Feng
CF
Basar
Murat
M
Kayisli
Umit A
UA
Martel
Maritza
M
Buhimschi
Irina
I
Buhimschi
Catalin
C
Huang
S Joseph
SJ
Krikun
Graciela
G
Schatz
Frederick
F
D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003656:Decidua / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy
D016207:Cytokines; D015850:Interleukin-6