Nuclear factor-kappa B is constitutively activated in peritoneal endometriosis

Reinaldo González-Ramos, González-Ramos R, Jacques Donnez, Donnez J, Defrère S, Sylvie Defrère, Leclercq I, Isabelle Leclercq, Squifflet J, Jean Squifflet, Lousse JC, Jean‐Christophe Lousse, Jean-Christophe Lousse, Van Langendonckt A, Anne Van Langendonckt
Molecular human reproduction · 2007 · vol. 13(7) , pp. 503–509 · doi:10.1093/molehr/gam033 · PMID:17483545 · W2114439418
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Constitutive nuclear factor-kappa B (NF-kappaB) activation, particularly involving p65 and p50 subunits, was demonstrated in peritoneal endometriosis, with higher levels and ICAM-1 expression in red lesions compared to black lesions.

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Abstract

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

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Condition tags

endometriosis

MeSH descriptors

Endometriosis NF-kappa B Peritoneal Diseases Peritoneum Adolescent Adult Endometriosis Endometriosis Female Humans I-kappa B Proteins I-kappa B Proteins Intercellular Adhesion Molecule-1 Intercellular Adhesion Molecule-1 NF-kappa B NF-KappaB Inhibitor alpha Peritoneal Diseases Peritoneal Diseases Peritoneum Peritoneum

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