Interleukin-33 modulates inflammation in endometriosis

Sci Rep. 2017 Dec 20;7(1):17903. doi: 10.1038/s41598-017-18224-x.

Abstract

Endometriosis is a debilitating condition that is categorized by the abnormal growth of endometrial tissue outside the uterus. Although the pathogenesis of this disease remains unknown, it is well established that endometriosis patients exhibit immune dysfunction. Interleukin (IL)-33 is a danger signal that is a critical regulator of chronic inflammation. Although plasma and peritoneal fluid levels of IL-33 have been associated with deep infiltrating endometriosis, its contribution to the disease pathophysiology is unknown. We investigated the role of IL-33 in the pathology of endometriosis using patient samples, cell lines and a syngeneic mouse model. We found that endometriotic lesions produce significantly higher levels of IL-33 compared to the endometrium of healthy, fertile controls. In vitro stimulation of endometrial epithelial, endothelial and endometriotic epithelial cells with IL-33 led to the production of pro-inflammatory and angiogenic cytokines. In a syngeneic mouse model of endometriosis, IL-33 injections caused systemic inflammation, which manifested as an increase in plasma pro-inflammatory cytokines compared to control mice. Furthermore, endometriotic lesions from IL-33 treated mice were highly vascularized and exhibited increased proliferation. Collectively, we provide convincing evidence that IL-33 perpetuates inflammation, angiogenesis and lesion proliferation, which are critical events in the lesion survival and progression of endometriosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascitic Fluid / metabolism
  • Ascitic Fluid / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Disease Models, Animal
  • Endometriosis / metabolism*
  • Endometriosis / pathology*
  • Endometrium / metabolism
  • Endometrium / pathology
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Inflammation / metabolism*
  • Inflammation / pathology*
  • Interleukin-33 / metabolism*
  • Interleukin-8 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology

Substances

  • Cytokines
  • IL33 protein, human
  • Interleukin-33
  • Interleukin-8