Heparin inhibits interferon-γ signaling in human endometrial stromal cells by interference with the cellular binding of interferon-γ

Objective: To examine the impact of heparins on interferon-gamma (IFN-gamma) signaling in human endometrial stromal cells (ESCs) in vitro. Design: In vitro experiment. Setting: Research laboratory at a medical university center. Patient(s): Premenopausal women undergoing hysterectomy for benign reasons. Intervention(s): The ESCs were isolated from hysterectomy specimens, decidualized in vitro using P and 17 beta-E-2, and incubated with recombinant IFN-gamma, unfractionated heparin, and low molecular weight heparins (LMWHs). Main Outcome Measure(s): Interferon response factor 1 (IRF-1) and N-myc interactor (Nmi) messenger RNA (mRNA) were measured using real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Phosphorylation of signal transducer and activator of transcription 1 (STAT-1) was detected by an in-cell Western assay, expression of the IFN-gamma receptor by flow cytometry. Cell-bound IFN-gamma was determined in lysates by an ELISA. Result(s): Heparin and LMWHs inhibit the IFN-gamma-mediated induction of IRF-1, but not Nmi in undifferentiated and decidualized ESCs. The phosphorylation of signal transducer and activator of transcription 1 STAT-1 upon IFN-gamma stimulation is inhibited as well. Heparin has no effect on the IFN-gamma receptor in ESCs, but inhibits the binding of IFN-gamma to the cells. Conclusion(s): Unfractionated heparin, as well as LMWHs, are able to inhibit IFN-gamma signaling in human ESCs and therefore might be clinically interesting agents to modulate the actions of this proinflammatory cytokine at the implantation site. (Fertil Steril (R) 2011;95:1272-7. (C) 2011 by American Society for Reproductive Medicine.)