Abstract | BACKGROUND: 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.
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Authors | Reinaldo González-Ramos, Anne Van Langendonckt, Sylvie Defrère, Jean-Christophe Lousse, Marcel Mettlen, Alain Guillet, Jacques Donnez |
Journal | Gynecologic and obstetric investigation
(Gynecol Obstet Invest)
Vol. 65
Issue 3
Pg. 174-86
( 2008)
ISSN: 1423-002X [Electronic] Switzerland |
PMID | 18025832
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- BAY 11-7085
- Enzyme Inhibitors
- NF-kappa B
- Nitriles
- Peptides
- SN50 peptide
- Sulfones
- Intercellular Adhesion Molecule-1
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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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