Agents blocking the nuclear factor-κB pathway are effective inhibitors of endometriosis in an in vivo experimental model

Reinaldo González-Ramos, Anne Van Langendonckt, Sylvie Defrère, Jean Christophe Lousse, Marcel Mettlen, Alain Guillet, Jacques Donnez

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Background: In vitro studies suggest that the transcription factor nuclear factor-kappa B (NF-κB) is implicated in the transduction of proinflammatory signals in endometriosis. The aim of this study was to investigate the involvement of NF-κB and the processes regulated by NF-κB in the initial development of endometriotic lesionsin vivo.Methods: Endometriosis was induced in nude mice by intraperitoneal injection of fluorescent-labeled menstrual endometrium. Two NF-κB inhibitors (BAY 11-7085 and SN-50) were injected intraperitoneally on days 0, 2 and 4 after endometriosis induction, and endometriotic lesions were recovered on day 5. Number, mass, fluorimetry and surface (morphometry) of endometriotic lesions were quantified. NF-κB activation, intercellular adhesion molecule (ICAM)-1 expression, cell proliferation and apoptosis were evaluated by immunohistochemical analyses and the TUNEL method. Results: Both NF-κB inhibitors induced a significant reduction in lesion development compared to control mice. NF-κB activation and ICAM-1 expression of endometriotic lesions were significantly reduced in treated mice, and cell proliferation was significantly reduced in BAY 11-7085-treated mice. Both inhibitors produced a significant increase in apoptosis of endometriotic lesions, as assessed by active caspase-3 immunostaining and the TUNEL method. Conclusion: This study demonstrates, for the first time, that the NF-κB pathway is implicated in the development of endometriotic lesions in vivo and that NF-κB inhibition reduces ICAM-1 expression and cell proliferation, but increases apoptosis of endometriotic lesions, diminishing the initial development of endometriosis in an animal model.

Original languageEnglish (US)
Pages (from-to)174-186
Number of pages13
JournalGynecologic and Obstetric Investigation
Volume65
Issue number3
DOIs
StatePublished - Apr 25 2008

Keywords

  • Apoptosis
  • BAY 11-7085
  • Cell proliferation
  • Endometriosis
  • ICAM-1/NF-κB inhibition
  • Inflammatory response
  • Nude mouse model
  • SN-50

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Fingerprint Dive into the research topics of 'Agents blocking the nuclear factor-κB pathway are effective inhibitors of endometriosis in an in vivo experimental model'. Together they form a unique fingerprint.

  • Cite this