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Activin A Stimulates Interleukin 8 and Vascular Endothelial Growth Factor Release From Cultured Human Endometrial Stromal Cells: Possible Implications for the Pathogenesis of Endometriosis

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Abstract

Background

Activin A is an endometrial secretory product involved in inflammation and angiogenesis. The present study aimed to evaluate the effect of activin A and its antagonist follistatin on interleukin (IL)-6, IL-8, and vascular endothelial growth factor (VEGF) expression and release from cultured human endometrial stromal cells (HESCs) from women with and without endometriosis.

Methods

The HESCs were collected from women with endometriosis (n = 6) and controls (n = 6). Primary cultures were treated with activin A at different doses or activin A plus follistatin. The IL-6, IL-8, and VEGF messenger RNA expression was evaluated by real-time polymerase chain reaction and protein release was evaluated by enzyme-linked immunosorbent assay.

Results

Unstimulated HESC from women with endometriosis secreted more IL-6 and IL-8 than controls. The addition of activin A increased IL-8 and VEGF secretion in HESC from controls and decreased IL-6 and IL-8 secretion in HESC from women with endometriosis. These effects were counteracted by follistatin.

Conclusion

Activin A regulates the expression and secretion of IL-8 and VEGF in cultured HESC, and this mechanism appears to be disrupted in eutopic endometrial cells from women affected by endometriosis.

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Authors and Affiliations

  1. Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Policlinico “Santa Maria alle Scotte”, Viale Bracci, 53100, Siena, Italy

    Ana Luiza L. Rocha MD, Patrizia Carrarelli BSc, Romina Novembri BSc, Flavio de Pascalis BSc, Stefano Luisi MD, PhD, Fernando M. Reis MD, PhD & Felice Petraglia MD, FRCOG

  2. Department of Obstetrics and Gynecology, Federal University of Minas Gerais, and National Institute of Hormones and Women’s Health, Belo Horizonte, Brazil

    Fernando M. Reis MD, PhD

Authors
  1. Ana Luiza L. Rocha MD
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  2. Patrizia Carrarelli BSc
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  3. Romina Novembri BSc
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  4. Flavio de Pascalis BSc
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  5. Stefano Luisi MD, PhD
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  6. Fernando M. Reis MD, PhD
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  7. Felice Petraglia MD, FRCOG
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Corresponding author

Correspondence to Felice Petraglia MD, FRCOG.

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Rocha, A.L.L., Carrarelli, P., Novembri, R. et al. Activin A Stimulates Interleukin 8 and Vascular Endothelial Growth Factor Release From Cultured Human Endometrial Stromal Cells: Possible Implications for the Pathogenesis of Endometriosis. Reprod. Sci. 19, 832–838 (2012). https://doi.org/10.1177/1933719111434542

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