Heparin modulates chemokines in human endometrial stromal cells by interaction with tumor necrosis factor α and thrombin

Unfractionated and low-molecular-weight heparins differentially modulate the stimulating effect of tumor necrosis factor a and thrombin on chemokines in human endometrial stromal cells in vitro.

Julia Spratte, M.D., Magdalena Schönborn, B.S., Nora Treder, B.S., Frauke Bornkessel, B.S., Marek Zygmunt, M.D., Ph.D., Herbert Fluhr, M.D., Ph.D.

Volume 103, Issue 5, Pages 1363-1369


To study the impact of heparins on chemokines in decidualized human endometrial stromal cells (ESCs) in vitro.

In vitro experiment.

Research laboratory.

Premenopausal women undergoing hysterectomy for benign reasons.

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.

Main Outcome Measure(s):
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.

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.

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.

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