Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis

Am J Reprod Immunol. 2013 Dec;70(6):497-508. doi: 10.1111/aji.12161. Epub 2013 Oct 3.

Abstract

Problem: We evaluated whether the expression of NF-кB p65 subunit is increased in the eutopic endometrium and/or in the ovarian endometrioma of women with advanced stage endometriosis, and ascertained in vitro effects of proinflammatory cytokines on the expression and DNA binding of NF-кB p65 subunit in endometrial cells.

Method of study: Immunohistochemistry was performed to compare the nuclear NF-кB p65 subunit immunoreactivity between women with and without advanced stage endometriosis. The nuclear NF-кB p65 subunit expression and DNA binding were also analyzed in endometrial cells treated with tumor necrosis factor-alpha (TNF-α) or interleukin-1beta (IL-1β) utilizing Western blot analysis, enzyme-linked immunosorbent assay, and electrophoretic mobility shift assay.

Results: The immunoreactivity of the nuclear NF-кB p65 subunit was significantly increased in the eutopic endometrium as well as in the ovarian endometrioma of women with endometriosis compared with the controls. In vitro treatment of endometrial cells with TNF-α and IL-1β led to a significant increase in nuclear NF-кB p65 subunit expression and DNA binding.

Conclusions: The nuclear expression of NF-κB p65 is increased in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis, which strongly suggests that NF-кB signaling plays a crucial role in the pathogenesis and/or pathophysiology of endometriosis.

Keywords: Cytokines; endometriosis; endometrium; nuclear factor kappa-B (NF-κB); p65 subunit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Nucleus / drug effects
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cells, Cultured
  • Endometriosis / genetics
  • Endometriosis / metabolism*
  • Endometriosis / pathology
  • Endometrium / metabolism*
  • Endometrium / pathology
  • Female
  • Humans
  • Interleukin-1beta / pharmacology
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Transcription Factor RelA / biosynthesis
  • Transcription Factor RelA / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Young Adult

Substances

  • Interleukin-1beta
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha