title: Agents blocking the nuclear factor-kappaB pathway are effective inhibitors of endometriosis in an in vivo experimental model.
abstract: BACKGROUND
  In vitro studies suggest that the transcription factor nuclear factor-kappa B (NF-kappaB) is implicated in the transduction of proinflammatory signals in endometriosis. The aim of this study was to investigate the involvement of NF-kappaB and the processes regulated by NF-kappaB 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-kappaB 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-kappaB activation, intercellular adhesion molecule (ICAM)-1 expression, cell proliferation and apoptosis were evaluated by immunohistochemical analyses and the TUNEL method.
  
  
  RESULTS
  Both NF-kappaB inhibitors induced a significant reduction in lesion development compared to control mice. NF-kappaB 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.
  
  
  CONCLUSIONS
  This study demonstrates, for the first time, that the NF-kappaB pathway is implicated in the development of endometriotic lesions in vivo and that NF-kappaB inhibition reduces ICAM-1 expression and cell proliferation, but increases apoptosis of endometriotic lesions, diminishing the initial development of endometriosis in an animal model.
authors.affiliation: Department of Gynecology, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Reinaldo
authors.initials: R
authors.lastname: González-Ramos
authors.forename: Anne
authors.initials: A
authors.lastname: Van Langendonckt
authors.forename: Sylvie
authors.initials: S
authors.lastname: Defrère
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Lousse
authors.forename: Marcel
authors.initials: M
authors.lastname: Mettlen
authors.forename: Alain
authors.initials: A
authors.lastname: Guillet
authors.forename: Jacques
authors.initials: J
authors.lastname: Donnez
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy* / Q000209:etiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009570:Nitriles / Q000627:therapeutic use*; D010455:Peptides / Q000627:therapeutic use*; D013450:Sulfones / Q000627:therapeutic use*
chemical_list: C416282:BAY 11-7085; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D009570:Nitriles; D010455:Peptides; C118258:SN50 peptide; D013450:Sulfones; D018799:Intercellular Adhesion Molecule-1