Agents Blocking the Nuclear Factor-κB Pathway Are Effective Inhibitors of Endometriosis in an in vivo Experimental Model

Gynecologic and Obstetric Investigation - Tập 65 Số 3 - Trang 174-186 - 2008
Reinaldo González-Ramos1, Anne Van Langendonckt1, Sylvie Defrère1, Jean‐Christophe Lousse1, Marcel Mettlen2, Alain Guillet3, Jacques Donnez1
1Department of Gynecology, Université Catholique de Louvain,
2CELL Unit, Université Catholique de Louvain and Christian de Duve Institute of Cellular Pathology, Brussels, and
3Institute of Statistics, Université catholique de Louvain, Louvain-la-Neuve, Belgium

Tóm tắt

<i>Background:</i> In vitro studies suggest that the transcription factor nuclear factor-kappa B (NF-ĸB) is implicated in the transduction of proinflammatory signals in endometriosis. The aim of this study was to investigate the involvement of NF-ĸB and the processes regulated by NF-ĸB in the initial development of endometriotic lesionsin vivo<i>.</i><i>Methods:</i> Endometriosis was induced in nude mice by intraperitoneal injection of fluorescent-labeled menstrual endometrium. Two NF-ĸB 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-ĸB activation, intercellular adhesion molecule (ICAM)-1 expression, cell proliferation and apoptosis were evaluated by immunohistochemical analyses and the TUNEL method. <i>Results:</i> Both NF-ĸB inhibitors induced a significant reduction in lesion development compared to control mice. NF-ĸB 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. <i>Conclusion:</i> This study demonstrates, for the first time, that the NF-ĸB pathway is implicated in the development of endometriotic lesions in vivo and that NF-ĸB 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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Gynecologic and Obstetric Investigation

Tập 65 Số 3

174-186

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