New insights into the pathophysiology of endometriosis: from chronic inflammation to danger signal.
BACKGROUND
Various theories try to explain the development and progression of endometriosis, however, no single theory can explain all aspects of this disorder. Gene expression profiling studies might reveal factors that explain variability in disease development and progression, which can serve as specific biomarkers for endometriosis and novel drug development. We have recently showed that the upregulated genes were predominantly clustered in stress and detoxification, providing a mechanistic explanation for the oxidative stress and chronic inflammatory response in endometriosis.


OBJECTIVE
This review aims: (1) to analyse the published data, with the aim of identifying pathways consistently regulated by the endometriosis genotype and (2) to summarise the findings of specific genes, which are involved in the process of oxidative stress and inflammation.


METHODS
We identified gene array and proteomics studies whose data were accessible in PubMed.


RESULTS
A major finding is the increased expressions of several markers including heat shock protein, S100, fibronectin, and neutrophil elastase, which might be involved in the process of Toll-like receptor (TLR)-dependent sterile inflammation. The study reviews a convergence in the main pathogenic process, where the TLR-mediated inflammation occurs possibly through the endogenous ligands.


CONCLUSIONS
In conclusion, a circulus vitiosus of both the oxidative stress pathway and the TLR pathways is generated when the process becomes chronic (danger signal spiral).
Kajihara
Hirotaka
H
Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan.
Yamada
Yoshihiko
Y
Kanayama
Seiji
S
Furukawa
Naoto
N
Noguchi
Taketoshi
T
Haruta
Shoji
S
Yoshida
Shozo
S
Sado
Toshiyuki
T
Oi
Hidekazu
H
Kobayashi
Hiroshi
H
D002908:Chronic Disease; D018450:Disease Progression; D004715:Endometriosis / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000235:genetics / Q000473:pathology; D008954:Models, Biological; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014591:Uterine Diseases / Q000209:etiology* / Q000235:genetics / Q000473:pathology
D051193:Toll-Like Receptors