Nuclear factor-kappa B is constitutively activated in peritoneal endometriosis

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