Insights into iron and nuclear \nfactor-kappa B (NF-κB) involvement in chronic \ninflammatory processes in peritoneal endometriosis

Endometriosis is a chronic pelvic \ninflammatory process. Local inflammation is known to \nplay a role in pain and infertility associated with the \ndisease, and may be extensively involved in molecular \nand cellular processes leading to endometriosis \ndevelopment. In this review, we focus on two \ninflammatory mediators clearly implicated in the \npathogenesis of endometriosis, iron and NF-κB, and \ntheir potential association. Iron is essential for all living \norganisms, but excess iron results in toxicity and is \nlinked to pathological disorders. In endometriosis \npatients, iron overload has been demonstrated in the \ndifferent compartments of the peritoneal cavity \n(peritoneal fluid, endometriotic lesions, peritoneum and \nmacrophages). This iron overload affects numerous \nmechanisms involved in endometriosis development. \nMoreover, iron can generate free radical species able to \nreact with a wide range of cellular constituents, inducing \ncellular damage. Overproduction of reactive oxygen \nspecies also impairs cellular function by altering gene \nexpression via regulation of redox-sensitive transcription \nfactors such as NF-κB, which is clearly implicated in \nendometriosis. Indeed, NF-κB is activated in \nendometriotic lesions and peritoneal macrophages of \nendometriosis patients, which stimulates synthesis of \nproinflammatory cytokines, generating a positive \nfeedback loop in the NF-κB pathway. NF-κB-mediated \ngene transcription promotes a variety of processes, \nincluding endometriotic lesion establishment, \nmaintenance and development. In conclusion, iron and NF-κB appear to be linked and both are clearly involved \nin endometriosis development, making these pathways \nan attractive target for future treatment and prevention of \nthis disease.