Lipopolysaccharide Appears to Activate Human Endometrial Endothelial Cells Through TLR-4-Dependent and TLR-4-Independent Mechanisms

Authors

  • Graciela Krikun,

    Corresponding author
    • Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
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  • Jordan Trezza,

    1. Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
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  • Jeff Shaw,

    1. Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
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  • Mizan Rahman,

    1. Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
    Current affiliation:
    1. Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, OH, USA
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  • Seth Guller,

    1. Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
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  • Vikki M. Abrahams,

    1. Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
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  • Charles J. Lockwood

    1. Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
    Current affiliation:
    1. Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, OH, USA
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Correspondence

Graciela Krikun, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, School of Medicine, LSOG 406, 333 Cedar Street, New Haven, CT 06510, USA.

E-mail: graciela.krikun@yale.edu

Abstract

Problem

Uterine innate immunity remains poorly characterized, and while endometrial endothelial cells are known to express Toll-like receptors (TLRs), little is known about their function in these cells. The present study evaluated the effect of Gram-negative bacterial lipopolysaccharide (LPS) on human endometrial endothelial cell (HEECs) cytokine secretion and tissue factor expression, and the role of TLR-4 in these responses.

Methods

Human endometrial endothelial cells were treated with or without LPS ± LPS-RS, a TLR-4 antagonist, via the binding of MD-2. After 24 hr, cell-free supernatants were evaluated for cytokines by multiplex analysis and cell lysates were analyzed for tissue factor expression by Western blot.

Results

Treatment of HEECs with LPS significantly upregulated the secretion of IL-6, IL-8, and G-CSF, and this was prevented by LPS-RS. LPS also induced tissue factor expression by the HEECs; however, this was unaffected by LPS-RS.

Conclusion

These findings suggest that TLR-4 is functional in HEECs and its activation by bacterial LPS induces a specific cytokine/chemokine response. However, bacterial LPS also induced tissue factor expression in what seemed to be a TLR-4-independent fashion, suggesting that this bacterial component can act on the HEECs through TLR-4-dependent and TLR-4-independent pathways. These findings indicate that endometrial endothelial cells may play an active role in uterine innate immunity.

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