title: The presence of heparins during decidualization modulates the response of human endometrial stromal cells to IL-1β in vitro.
abstract: OBJECTIVE
  The aim of this paper is to study the impact of heparin on the response of human endometrial stromal cells (ESCs) to interleukin (IL)-1β during decidualization in vitro.
  
  
  METHODS
  ESCs were isolated from hysterectomy specimens of premenopausal women undergoing hysterectomy for benign reasons; decidualized in vitro and incubated in parallel with unfractionated heparin or tinzaparin; and stimulated with IL-1β at days 0, 3, 6, and 9 during decidualization. IL-6, IL-11, and leukemia inhibitory factor (LIF) were analyzed using ELISAs and real-time RT-PCR. Cell viability was determined by a fluorometric assay.
  
  
  RESULTS
  IL-1β dose-dependently stimulated IL-6, IL-11, and LIF in distinct patterns in ESCs during decidualization. Unfractionated heparin as well as tinzaparin attenuated the IL-1β-mediated induction of IL-6, IL-11, and LIF on protein and messenger RNA (mRNA) levels. The relative effects of heparin and tinzaparin were getting more pronounced during the time course of decidualization.
  
  
  CONCLUSIONS
  Unfractionated heparin and the low molecular weight heparin tinzaparin have modulating effects on IL-1β-induced endometrial cytokines of the IL-6 family during decidualization. These effects of heparins beyond their classical anti-coagulatory properties might have implications on the regulation of endometrial receptivity and early implantation.
authors.affiliation: Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany. julia.spratte@med.uni-heidelberg.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Spratte
authors.affiliation: Department of Obstetrics and Gynecology, University of Greifswald, Sauerbruchstr, 17475, Greifswald, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Bornkessel
authors.affiliation: Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schütz
authors.affiliation: Department of Obstetrics and Gynecology, University of Greifswald, Sauerbruchstr, 17475, Greifswald, Germany.
authors.forename: Marek
authors.initials: M
authors.lastname: Zygmunt
authors.affiliation: Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Fluhr
mesh_terms: D002470:Cell Survival; D003656:Decidua / Q000196:embryology*; D010064:Embryo Implantation; D004717:Endometrium / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D007044:Hysterectomy; D017370:Interleukin-11 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D000078222:Tinzaparin
chemical_list: D006495:Heparin, Low-Molecular-Weight; C508611:IL11 protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; D017370:Interleukin-11; D053583:Interleukin-1beta; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D000078222:Tinzaparin; D006493:Heparin
keywords: Cytokines; Decidualization; Heparin; IL-1β