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

Capsule:
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.

Authors:
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

Abstract:

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

Design:
In vitro experiment.

Setting:
Research laboratory.

Patient(s):
Premenopausal women undergoing hysterectomy for benign reasons.

Intervention(s):
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.

Result(s):
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.

Conclusion(s):
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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