Mol. Hum. Reprod. Advance Access published online on May 5, 2007
Molecular Human Reproduction, doi:10.1093/molehr/gam033
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Nuclear factor-kappa B is constitutively activated in peritoneal endometriosis
1 Department of Gynecology, Université Catholique de Louvain, Cliniques Universitaires St Luc, Avenue Hippocrate 10, 1200 Brussels, Belgium 2 Department of Internal Medicine, Gastroenterology Unit, Université Catholique de Louvain, Brussels, Belgium
3 Correspondence address. Tel: +32-2-764-95-01; Fax: +32-2-764-95-07; E-mail: donnez{at}gyne.ucl.ac.be
Red (active), black and white endometriotic lesions are characteristic of peritoneal endometriosis. The transcription factor nuclear factor-kappa B (NF-
B) activates proinflammatory, proliferative and antiapoptotic genes in many cell types. To determine whether NF-B is activated in peritoneal endometriosis in women, and further ascertain the differential inflammatory status of endometriotic implants, NF-B activation and intercellular adhesion molecule (ICAM)-1 expression were investigated in peritoneal endometriotic lesions according to their type. Furthermore, p65 and p50 subunits of active NF-B dimers were evaluated in endometriotic lesions to gain some insight into NF-B-implicated pathways. Thirty-six biopsies of peritoneal endometriotic lesions were analyzed. Constitutive NF-B activation, involving p65- and p50-containing dimers, was demonstrated in peritoneal endometriotic lesions by electrophoretic mobility shift assays and supershift analyses, as well as NF-B (p65) DNA-binding activity immunodetection assays. NF-B activation and ICAM-1 expression (evaluated by immunoblotting) were significantly higher in red lesions than black lesions, whereas IB
(NF-B inhibitory protein) expression was constant, as shown by western blot analysis. This is the first study to demonstrate constitutive NF-B activation in peritoneal endometriosis in women. NF-B activation and ICAM-1 expression in red lesions confirm the more extensive inflammatory pattern of these lesions compared with black lesions. The involvement of p50/p65 dimers in NF-B activation suggests implication of the classic NF-B activation pathway, making it an attractive therapeutic target in endometriosis.
Key Words: endometriosis/ICAM-1/IkappaB/inflammation/NF-kappaB
Submitted on February 28, 2007; resubmitted on March 23, 2007; accepted on March 26, 2007.
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