Immunopathogenesis of pelvic endometriosis: role of hepatocyte growth factor, macrophages and ovarian steroids.
Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology of endometriosis is still elusive. It is generally believed that besides ovarian steroid hormones, the growth of endometriosis can be regulated by innate immune system in pelvic microenvironment by their interaction with endometrial cells and immune cells. We conducted a series of studies in perspectives of pelvic inflammation that is triggered primarily by bacterial endotoxin (lipopolysaccharide) and is mediated by toll-like receptor 4 and showed their involvement in the development of pelvic endometriosis. As a cellular component of innate immune system, macrophages were found to play a central role in inducing pelvic inflammatory reaction. We further report here that peritoneal macrophages retain receptors encoding for estrogen and progesterone and ovarian steroids also participate in producing an inflammatory response in pelvic cavity and are involved in the growth of endometriosis either alone or in combination with hepatocyte growth factor (HGF). As a pleiotropic growth factor, HGF retains multifunctional role ometriosis. We describe here the individual and step-wise role of HGF, macrophages and ovarian steroid hormones and their orchestrated involvement in the immunopathogenesis of pelvic endometriosis.
Khan
Khaleque Newaz
KN
Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. nemokhan@nagasaki-u.ac.jp
Kitajima
Michio
M
Hiraki
Koichi
K
Fujishita
Akira
A
Sekine
Ichiro
I
Ishimaru
Tadayuki
T
Masuzaki
Hideaki
H
D015820:Cadherins / Q000276:immunology / Q000378:metabolism; D004715:Endometriosis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D004967:Estrogens / Q000276:immunology / Q000378:metabolism*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D010053:Ovary / Q000276:immunology / Q000378:metabolism; D010388:Pelvis; D011374:Progesterone / Q000276:immunology / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism
D015820:Cadherins; D004967:Estrogens; D016023:Integrins; D051197:Toll-Like Receptor 4; D011374:Progesterone; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met