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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Activin A stimulation increased IL-8 and VEGF secretion in control endometrial stromal cells but decreased IL-6 and IL-8 in cells from women with endometriosis.

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The study investigated how activin A and its antagonist follistatin affect inflammatory and angiogenic signaling (IL-6, IL-8, and VEGF) in cultured human endometrial stromal cells (HESCs) collected from women with endometriosis (n=6) and without endometriosis (n=6), using real-time PCR for mRNA and ELISA for protein release. Unstimulated HESCs from women with endometriosis secreted higher IL-6 and IL-8 than controls. Activin A increased IL-8 and VEGF secretion in control HESCs but decreased IL-6 and IL-8 secretion in endometriosis-derived HESCs, and these effects were counteracted by follistatin. The authors’ key limitation is the small sample size and in vitro cultured-cell context. This paper is centrally about endometriosis — it tests whether activin A–dependent regulation of IL-8 and VEGF release in eutopic endometrial stromal cells is altered in women with 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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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. Similar content being viewed by others

References

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Interferon gamma(IFN-g) and interleukin-6 (IL-6) in peritoneal fluid and macrophage- conditioned media of women with endometriosis. Am J Reprod Immunol. 1994;32(3):180–183. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article 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 Published: Issue date: DOI: https://doi.org/10.1177/1933719111434542

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Condition tags

endometriosis

MeSH descriptors

Activins Endometriosis Endometrium Gene Expression Regulation Interleukin-8 Vascular Endothelial Growth Factor A Activins Activins Adult Cells, Cultured Endometriosis Endometriosis Endometrium Endometrium Endometrium Female Follistatin Follistatin Gene Expression Regulation Humans

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