Insights into iron and nuclear factor-kappa B (NF-κB) involvement in chronic inflammatory processes in peritoneal endometriosis
Sylvie Defrère1, Reinaldo González-Ramos2, Jean-Christophe Lousse1, Sébastien Colette1, Olivier Donnez1, Jacques Donnez1 and Anne Van Langendonckt1
1Université Catholique de Louvain, Institute of Experimental and Clinical Research, Department of Gynecology, Brussels, Belgium and 2Institute of Maternal and Child Research, Obstetrics and Gynecology Department, San Borja-Arriaran Clinical Hospital, School of Medicine, University of Chile, Santiago, Chile.
Offprint requests to: Professor Jacques Donnez, Department of Gynecology, Université catholique de Louvain, Cliniques Universitaires St Luc, Avenue Hippocrate 10, 1200 Brussels, Belgium. e-mail: jacques.donnez@uclouvain.be
Summary. Endometriosis is a chronic pelvic inflammatory process. Local inflammation is known to play a role in pain and infertility associated with the disease, and may be extensively involved in molecular and cellular processes leading to endometriosis development. In this review, we focus on two inflammatory mediators clearly implicated in the pathogenesis of endometriosis, iron and NF-κB, and their potential association. Iron is essential for all living organisms, but excess iron results in toxicity and is linked to pathological disorders. In endometriosis patients, iron overload has been demonstrated in the different compartments of the peritoneal cavity (peritoneal fluid, endometriotic lesions, peritoneum and macrophages). This iron overload affects numerous mechanisms involved in endometriosis development. Moreover, iron can generate free radical species able to react with a wide range of cellular constituents, inducing cellular damage. Overproduction of reactive oxygen species also impairs cellular function by altering gene expression via regulation of redox-sensitive transcription factors such as NF-κB, which is clearly implicated in endometriosis. Indeed, NF-κB is activated in endometriotic lesions and peritoneal macrophages of endometriosis patients, which stimulates synthesis of proinflammatory cytokines, generating a positive feedback loop in the NF-κB pathway. NF-κB-mediated gene transcription promotes a variety of processes, including endometriotic lesion establishment, maintenance and development. In conclusion, iron and NF-κB appear to be linked and both are clearly involved in endometriosis development, making these pathways an attractive target for future treatment and prevention of this disease. Histol Histopathol 26, 1083-1092 (2011)
Key words: Endometriosis, Inflammation, Iron, NF-kappaB, Macrophage
DOI: 10.14670/HH-26.1083