title: Thrombin regulates monocyte chemoattractant protein-1 expression in human first trimester and term decidual cells.
abstract: OBJECTIVE
  Excess decidual macrophage infiltration has been linked to preeclampsia and a failure of endovascular trophoblast invasion. Severe preeclampsia with shallow placentation has also been linked to acquired and inherited maternal thrombophilias and recurrent decidual hemorrhage, which generates thrombin from decidual cell-expressed tissue factor. Therefore, the current study evaluated whether thrombin affects monocyte chemoattractant protein-1 (MCP-1) expression in stromal cells that are derived from cycling and gestational endometrium.
  
  
  METHODS
  Stromal cells that are isolated from cycling endometrium and first trimester and term decidua were grown to confluence, treated for 7 days with 10(-8) mol/L estradiol (E2) + 10(-7) mol/L medroxyprogesterone acetate (MPA), then switched to a serum-free medium that contained the corresponding steroids +/- thrombin. MCP-1 protein release was measured by enzyme-linked immunosorbent assay and Western blot; MCP-1 messenger RNA levels were assessed by real-time quantitative reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  Secreted MCP-1 levels were not significantly different in stromal or decidual cell cultures that were incubated with E2 or with E2 + MPA. Thrombin increased immunoreactive MCP-1 expression in a dose-response fashion in first trimester and term decidual cells but not in endometrial stromal cells. Thrombin-induced MCP-1 protein output was unaffected by MPA but was abrogated by incubation with the thrombin inhibitor, hirudin. Unexpectedly, thrombin-enhanced MCP-1 protein expression was unaccompanied by corresponding changes in steady state MCP-1 messenger RNA levels, which suggests its effects were posttranslational.
  
  
  CONCLUSIONS
  MCP-1 protein expression is up regulated by thrombin in decidual cells across gestation, but not in stromal cells from predecidualized cycling endometrium.
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Matta
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lockwood
authors.forename: Frederick
authors.initials: F
authors.lastname: Schatz
authors.forename: Graciela
authors.initials: G
authors.lastname: Krikun
authors.forename: Mizanur
authors.initials: M
authors.lastname: Rahman
authors.forename: Lynn
authors.initials: L
authors.lastname: Buchwalder
authors.forename: Errol R
authors.initials: ER
authors.lastname: Norwitz
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D003656:Decidua / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D047929:Term Birth; D013917:Thrombin / Q000502:physiology*
chemical_list: D018932:Chemokine CCL2; D013917:Thrombin