title: Heparin modulates chemokines in human endometrial stromal cells by interaction with tumor necrosis factor α and thrombin.
abstract: OBJECTIVE
  To study the impact of heparins on chemokines in decidualized human endometrial stromal cells (ESCs) in vitro.
  
  
  METHODS
  In vitro experiment.
  
  
  METHODS
  Research laboratory.
  
  
  METHODS
  Premenopausal women undergoing hysterectomy for benign reasons.
  
  
  METHODS
  ESCs were isolated from hysterectomy specimens, decidualized in vitro and incubated with unfractionated heparin and low-molecular-weight heparins (LMWHs) as well as tumor necrosis factor (TNF) α or thrombin with or without heparins.
  
  
  METHODS
  Chemokines CXCL1, CXCL5, CXCL8, CCL2, and CCL5 were measured with the use of ELISA, and CXCL5, CXCL8, CCL2, and CCL5 were detected with the use of real-time reverse-transcription polymerase chain reaction. Cell viability was determined with the use of a fluorometric assay.
  
  
  RESULTS
  TNF-α and thrombin stimulated distinct patterns of chemokines in ESCs. Unfractionated heparin and LMWHs attenuated the TNF-α-mediated induction of CXCL8 and enhanced CXCL5, CCL2, and CCL5. The stimulating effect of thrombin on CXCL8 could be inhibited by heparin, whereas heparin had no impact on thrombin-induced CXCL1 and CCL2. Nuclear factor of transcription κB signaling mediated the effects of TNF-α. The effects of thrombin were mediated via extracellular signal-regulated protein kinases 1/2.
  
  
  CONCLUSIONS
  Heparins have modulating effects on TNF-α- and thrombin-induced endometrial chemokines, which might have implications in the regulation of endometrial receptivity and early implantation.
authors: Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany. Electronic address: julia.spratte@med.uni-heidelberg.de.
authors: Julia
authors: J
authors: Spratte
authors: Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany.
authors: Magdalena
authors: M
authors: Schönborn
authors: Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany.
authors: Nora
authors: N
authors: Treder
authors: Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany.
authors: Frauke
authors: F
authors: Bornkessel
authors: Department of Obstetrics and Gynecology, University of Greifswald, Greifswald, Germany.
authors: Marek
authors: M
authors: Zygmunt
authors: Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
authors: Herbert
authors: H
authors: Fluhr
mesh_terms: D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004717:Endometrium / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D018925:Chemokines; D006495:Heparin, Low-Molecular-Weight; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D006493:Heparin; D048049:Extracellular Signal-Regulated MAP Kinases; D013917:Thrombin
keywords: Heparin; TNF-α; chemokines; endometrium; thrombin