title: Interleukin-33 in the human placenta.
abstract: OBJECTIVE
  Interleukin-33 (IL-33) is the newest member of the IL-1 cytokine family, a group of key regulators of inflammation. The purpose of this study was to determine whether IL-33 is expressed in the human placenta and to investigate its expression in the context of acute and chronic chorioamnionitis.
  
  
  METHODS
  Placental tissues were obtained from five groups of patients: 1) normal pregnancy at term without labor (n = 10); 2) normal pregnancy at term in labor (n = 10); 3) preterm labor without inflammation (n = 10); 4) preterm labor with acute chorioamnionitis and funisitis (n = 10); and 5) preterm labor with chronic chorioamnionitis (n = 10). Immunostaining was performed to determine IL-33 protein expression patterns in the placental disk, chorioamniotic membranes, and umbilical cord. mRNA expression of IL-33 and its receptor IL1RL1 (ST2) was measured in primary amnion epithelial and mesenchymal cells (AECs and AMCs, n = 4) and human umbilical vein endothelial cells (HUVECs, n = 4) treated with IL-1β (1 and 10 ng/ml) and CXCL10 (0.5 and 1 or 5 ng/ml).
  
  
  RESULTS
  1) Nuclear IL-33 expression was found in endothelial and smooth muscle cells in the placenta, chorioamniotic membranes, and umbilical cord; 2) IL-33 was detected in the nucleus of CD14+ macrophages in the chorioamniotic membranes, chorionic plate, and umbilical cord, and in the cytoplasm of myofibroblasts in the Wharton's jelly; 3) acute (but not chronic) chorioamnionitis was associated with the presence of IL-33+ macrophages in the chorioamniotic membranes and umbilical cord; 4) expression of IL-33 or IL1RL1 (ST2) mRNA in AECs was undetectable; 5) IL-33 mRNA expression increased in AMCs and HUVECs after IL-1β treatment but did not change with CXCL10 treatment; and 6) IL1RL1 (ST2) expression decreased in AMCs and increased in HUVECs after IL-1β but not CXCL10 treatment.
  
  
  CONCLUSIONS
  IL-33 is expressed in the nucleus of placental endothelial cells, CD14+ macrophages, and myofibroblasts in the Wharton's jelly. IL-1β can induce the expression of IL-33 and its receptor. Protein expression of IL-33 is detectable in macrophages of the chorioamniotic membranes in acute (but not chronic) chorioamnionitis.
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD 20892, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Topping
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Nandor Gabor
authors.initials: NG
authors.lastname: Than
authors.forename: Adi L
authors.initials: AL
authors.lastname: Tarca
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Xu
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Lami
authors.initials: L
authors.lastname: Yeo
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000208:Acute Disease; D000650:Amnion / Q000098:blood supply / Q000737:chemistry; D002467:Cell Nucleus / Q000737:chemistry; D002821:Chorioamnionitis / Q000378:metabolism; D002823:Chorion / Q000098:blood supply / Q000737:chemistry; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D042783:Endothelial Cells / Q000737:chemistry; D005260:Female; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000032:analysis* / Q000235:genetics; D007743:Labor, Obstetric / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008264:Macrophages / Q000737:chemistry / Q000648:ultrastructure; D059630:Mesenchymal Stem Cells / Q000648:ultrastructure; D007752:Obstetric Labor, Premature / Q000378:metabolism; D010920:Placenta / Q000737:chemistry*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics; D014471:Umbilical Veins / Q000737:chemistry
chemical_list: C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface