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Dose–response effect of interleukin (IL)-1β, tumour necrosis factor (TNF)-α, and interferon-γ on the in vitro production of epithelial neutrophil activating peptide-78 (ENA-78), IL-8, and IL-6 by human endometrial stromal cells

  • General Gynecology
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Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

The production of epithelial neutrophil activating peptide-78 (NA-78) and the interleukins IL-8 and IL-6 by endometrial stromal cells is stimulated by pro-inflammatory interleukin-1 (IL-1) and tumour necrosis factor-α (TNF-α). IL-8 is suggested to play a role in the pathogenesis of endometriosis, and in these women the peritoneal fluid concentrations of ENA-78 and IL-8 are increased. TNF-α has been tested together with interferon-γ because of their cooperative stimulation of IL-6. The release of IL-8, however, is inhibited with increasing interferon levels. The aim of the study was the analysis of the production of ENA-78, IL-6 and IL-8 by cultured human endometrial stromal cells in the presence of varying concentrations of IL-1β, TNF-α, and interferon-γ.

Methods

Eutopic endometrial tissue was obtained from seven cycling, endometriosis-free women undergoing laparoscopy for reasons of infertility or pain. The release of ENA-78, IL-8 and IL-6 by the isolated and monolayer cultured stromal cell fraction in the presence of IL-1β (0.08 to 50 ng/mL), TNF-α, and interferon-γ (both 20 to 500 ng/mL) was determined.

Results

IL-1β stimulated the production of IL-8, IL-6, and ENA-78 dose dependently from 0.08 to 2.0 ng/mL (ENA-78) or to 10 ng/mL (IL-8, IL-6); at 50 ng/mL a decrease in release was observed for IL-8 and IL-6. TNF-α stimulation yielded a plateau between 20 and 100 ng/mL. Interferon-γ stimulated IL-6 and inhibited IL-8 production above 20 ng/mL. ENA-78 release was largely unaffected by interferon-γ.

Conclusions

IL-1β and TNF-α stimulate stromal cytokine production cumulatively with different dose–response curves. The presence of interferon-γ has opposite effects on IL-8 and IL-6. TNF-α and interferon-γ should be investigated separately in future in vitro studies with endometrial cells and explants.

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Author notes

  1. Silke Johann

    Present address: Hôpital du jura bernois, St-Imier, Switzerland

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, University of Berne, Berne, Switzerland

    Nick A. Bersinger, Andreas R. Günthert & Michael D. Mueller

  2. Department of Clinical Research, University of Berne, Berne, Switzerland

    Nick A. Bersinger & Brett McKinnon

  3. University of Berne, Endometriosis and Human Reproduction, Research Laboratory, Inselspital, DKF Murtenstrasse 35, 3010, Berne, Switzerland

    Nick A. Bersinger

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  1. Nick A. Bersinger
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Correspondence to Nick A. Bersinger.

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Bersinger, N.A., Günthert, A.R., McKinnon, B. et al. Dose–response effect of interleukin (IL)-1β, tumour necrosis factor (TNF)-α, and interferon-γ on the in vitro production of epithelial neutrophil activating peptide-78 (ENA-78), IL-8, and IL-6 by human endometrial stromal cells. Arch Gynecol Obstet 283, 1291–1296 (2011). https://doi.org/10.1007/s00404-010-1520-3

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  • DOI: https://doi.org/10.1007/s00404-010-1520-3

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