Involvement of the nuclear factor-κB pathway in the pathogenesis of endometriosis.
OBJECTIVE
To evaluate the role of nuclear factor-κB (NF-κB) in the pathogenesis of endometriosis.


METHODS
A literature search was conducted in PubMed to identify all relevant citations.


RESULTS
Our findings highlight the important role of NF-κB in the pathophysiology of endometriosis. In vitro and in vivo studies show that NF-κB-mediated gene transcription promotes inflammation, invasion, angiogenesis, and cell proliferation and inhibits apoptosis of endometriotic cells. Constitutive activation of NF-κB has been demonstrated in endometriotic lesions and peritoneal macrophages of endometriosis patients. Agents blocking NF-κB are effective inhibitors of endometriosis development and some drugs with known NF-κB inhibitory properties have proved efficient at reducing endometriosis-associated symptoms in women. Iron overload activates NF-κB in macrophages. NF-κB activation in macrophages and ectopic endometrial cells stimulates synthesis of proinflammatory cytokines, generating a positive feedback loop in the NF-κB pathway and promoting endometriotic lesion establishment, maintenance and development.


CONCLUSIONS
NF-κB transcriptional activity modulates key cell processes contributing to the initiation and progression of endometriosis. Because endometriosis is a multifactorial disease, inhibiting NF-κB appears to be a promising strategy for future therapies targeting different cell functions involved in endometriosis development, such as cell adhesion, invasion, angiogenesis, inflammation, proliferation, and apoptosis. Upcoming research will elucidate these hypotheses.
González-Ramos
Reinaldo
R
Instituto de Investigaciones Materno Infantil, Departamento de Obstetricia y Ginecología, Hospital Clínico San Borja-Arriarán, Facultad de Medicina, Universidad de Chile, Santiago, Chile. rgonzalezr@med.uchile.cl
Van Langendonckt
Anne
A
Defrère
Sylvie
S
Lousse
Jean-Christophe
JC
Colette
Sebastien
S
Devoto
Luigi
L
Donnez
Jacques
J
D000818:Animals; D004715:Endometriosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014591:Uterine Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D016328:NF-kappa B