Preeclampsia-related increase of interleukin-11 expression in human decidual cells.
Preeclampsia is associated with increased systemic inflammation and superficial trophoblast invasion, which leads to insufficient uteroplacental blood flow. Interleukin (IL)-11 mediates pro- and anti-inflammatory processes and facilitates decidualization. To identify IL11 expression in vivo at the maternal-placental interface in preeclampsia and control specimens and to evaluate the regulatory effects of tumor necrosis factor-α (TNF) and IL1B, cytokines elevated in preeclampsia, on IL11 levels in first trimester decidual cells in vitro, placental sections were immunostained for IL11. Leukocyte-free first trimester decidual cells were incubated with estradiol (E(2))±10(-7)  mol/l medroxyprogesterone acetate±TNF or IL1B± inhibitors of the p38 MAP kinase (p38 MAPK), nuclear factor-κ B (NFKB), or protein kinase C (PKC) signaling pathways. An ELISA assessed secreted IL11 levels, and quantitative RT-PCR measured IL11 mRNA. IL11 immunoreactivity in placental sections was significantly higher in the cytoplasm of preeclamptic decidual cells versus gestational age-matched controls. Compared to decidual cells, IL11 immunostaining in neighboring trophoblast is lower, perivascular, and not different between control and preeclamptic specimens. TNF and IL1B enhanced levels of IL11 mRNA and secreted IL11 in cultured decidual cells. Specific inhibitors of the p38 MAPK and NFKB, but not PKC signaling pathways, reduced the stimulatory effect of IL1B. Expression of decidual IL11 is increased in preeclampsia and suggests a role for IL11 in the pathogenesis of preeclampsia.
Basar
Murat
M
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Yen
Chih-Feng
CF
Buchwalder
Lynn F
LF
Murk
William
W
Huang
S Joseph
SJ
Godlewski
Karl
K
Kocamaz
Erdogan
E
Arda
Oktay
O
Schatz
Frederick
F
Lockwood
Charles J
CJ
Kayisli
Umit A
UA
D000328:Adult; D003656:Decidua / Q000166:cytology / Q000276:immunology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D017370:Interleukin-11 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology; D009281:Naphthalenes / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000276:immunology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology
C508611:IL11 protein, human; D007093:Imidazoles; D017370:Interleukin-11; D053583:Interleukin-1beta; D016328:NF-kappa B; D009281:Naphthalenes; D011725:Pyridines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; C058819:calphostin C; C093642:SB 203580