Nuclear factor-kappa B is constitutively activated in peritoneal endometriosis

• Published in: Molecular human reproduction 2007-07, Vol.13 (7), p.503-509
• Main Authors: González-Ramos, Reinaldo, Donnez, Jacques, Defrère, Sylvie, Leclercq, Isabelle, Squifflet, Jean, Lousse, Jean-Christophe, Van Langendonckt, Anne
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; Embryology: invertebrates and vertebrates. Teratology; Endometriosis; Endometriosis - metabolism; Endometriosis - pathology; Female; Fundamental and applied biological sciences. Psychology; Humans; I-kappa B Proteins - metabolism; ICAM-1; IkappaB; inflammation; Intercellular Adhesion Molecule-1 - metabolism; NF-kappa B - metabolism; NF-kappaB; NF-KappaB Inhibitor alpha; Peritoneal Diseases - metabolism; Peritoneal Diseases - pathology; Peritoneum - metabolism; Peritoneum - pathology
• ISSN: 1360-9947; 1460-2407
• DOI: 10.1093/molehr/gam033

Red (active), black and white endometriotic lesions are characteristic of peritoneal endometriosis. The transcription factor nuclear factor-kappa B (NF-κB) activates proinflammatory, proliferative and antiapoptotic genes in many cell types. To determine whether NF-κB is activated in peritoneal endometriosis in women, and further ascertain the differential inflammatory status of endometriotic implants, NF-κB 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-κB dimers were evaluated in endometriotic lesions to gain some insight into NF-κB-implicated pathways. Thirty-six biopsies of peritoneal endometriotic lesions were analyzed. Constitutive NF-κB 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-κB (p65) DNA-binding activity immunodetection assays. NF-κB activation and ICAM-1 expression (evaluated by immunoblotting) were significantly higher in red lesions than black lesions, whereas IκBα (NF-κB inhibitory protein) expression was constant, as shown by western blot analysis. This is the first study to demonstrate constitutive NF-κB activation in peritoneal endometriosis in women. NF-κB 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-κB activation suggests implication of the classic NF-κB activation pathway, making it an attractive therapeutic target in endometriosis.