| Project/Area Number |
16591671
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Obstetrics and gynecology
|
|---|
| Research Institution | Nagasaki University |
|---|
Principal Investigator |
KHAN Khaleque Nagasaki University, Graduate School of Biomedical Sciences, Obstetrics and Gynecology, Assistant Professor, 大学院・医歯薬学総合研究科, 助手 (60336162)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FUJISHITA Akira Nagasaki University, Graduate School of Biomedical Sciences, Obstetrics and Gynecology, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (70190030)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | Endometriosis / Peritoneal fluid / Macrophages / Endotoxin / HGF / TLR4 |
|---|
| Research Abstract |
We demonstrated regulation of the growth of endometriosis by innate immune system and ovarian steroid hormones. As a cell component of endometriosis and innate immune system, we found a significantly increased infiltration of CD68-positive macrophages (Mφ) in the eutopic endometrium, ectopic endometrium and peritoneal fluid (PF) of women with endometriosis than that of non-endometriosis (Fertil Steril 81(3):652-661,2004). Bacterial endotoxin or lipopolysaccharide (LPS) acts as an initial inflammatory mediator and interacts with toll-like recpetor 4 (TLR) on Mφ and other dendritic cells and produces different proinflammatiry cytokines. We reported that Mφ isolated from women with endometriosis produced increased concentrations of cytokines and growth factors including HGF in response to LPS. As a pleiotropic growth factor, HGF either alone or in combination with LPS was involved in the growth of endometriosis in an autocrine and paracrine fashion (Hum Reprod 20:49-60,2005).
We also demon
… More
strated Mφ-mediated regulation of HGF by ovarian steroids in women with endometriosis. Estrogen (ER) and progesterone receptor (PR) were expressed in Mφ and endometrial cells at both protein and mRNA levels. Macrophages in response to estrogen produced higher concentrations of HGF and other cytokines and established that HGF may be involved in the growth of endometriosis either alone or together with estrogen (Hum Reprod 20(7):2004-2013,2005).
We reported for the time that endotoxin concentration in the PF was significantly higher in women with endometriosis than that in non-endometriosis. TLR4 was detected in Mφ and endometrial cells. Single or combined treatment of Mφ with LPS or Hsp70 produced significantly increased levels of HGF, VEGF, IL-6 and TNFα in women with endometriosis. Pretreatment of cells with anti-TLR4 antibody significantly reduced the production of all these cytokines as well as growth of endometriosis. Our results suggested that endotoxin in PF may promote TLR4-mediated growth of endometriosis.
It was very interesting to detect a significantly higher colony formation of Escherichia coli (E.coli) when we cultured menstrual blood of women with endometriosis than that in non-endmetriosis. This indicates that E.coli in menstrual blood could be a source of increased endotoxin in PF and consequently regulate TLR4-mediated growth of endometriosis. Less
|
