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. 2012 Aug;19(8):832-8. doi: 10.1177/1933719111434542. Epub 2012 Apr 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / antagonists & inhibitors
  • Activins / pharmacology*
  • Adult
  • Cells, Cultured
  • Endometriosis / etiology
  • Endometriosis / metabolism*
  • Endometrium / chemistry
  • Endometrium / drug effects
  • Endometrium / metabolism*
  • Female
  • Follistatin / pharmacology
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics*
  • Interleukin-8 / metabolism
  • RNA, Messenger / analysis
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Follistatin
  • Interleukin-6
  • Interleukin-8
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • activin A
  • Activins