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

AbstractBACKGROUND:
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.
CONCLUSION:
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.
AuthorsReinaldo González-Ramos, Anne Van Langendonckt, Sylvie Defrère, Jean-Christophe Lousse, Marcel Mettlen, Alain Guillet, Jacques Donnez
JournalGynecologic and obstetric investigation (Gynecol Obstet Invest) Vol. 65 Issue 3 Pg. 174-86 ( 2008) ISSN: 1423-002X [Electronic] Switzerland
PMID18025832 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • BAY 11-7085
  • Enzyme Inhibitors
  • NF-kappa B
  • Nitriles
  • Peptides
  • SN50 peptide
  • Sulfones
  • Intercellular Adhesion Molecule-1
Topics
  • Animals
  • Apoptosis (drug effects)
  • Cell Proliferation (drug effects)
  • Disease Models, Animal
  • Endometriosis (drug therapy, etiology)
  • Enzyme Inhibitors (therapeutic use)
  • Female
  • Humans
  • Intercellular Adhesion Molecule-1 (biosynthesis)
  • Mice
  • Mice, Nude
  • NF-kappa B (antagonists & inhibitors)
  • Nitriles (therapeutic use)
  • Peptides (therapeutic use)
  • Sulfones (therapeutic use)

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