Role of Bacterial Endotoxin and Innate Immune System in Endometriosis
Project/Area Number |
18591837
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Nagasaki University |
Principal Investigator |
KHAN Khaleque Nagasaki University, Department if Obstetrics and Gynecology, Assistant Professor (60336162)
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Co-Investigator(Kenkyū-buntansha) |
KITAJIMA Michio Nagasaki University, Dept. of Obstetrics and Gynecology, Assistant Professor (50380845)
KHAN Khaleque Nagasaki University, Dept. of Obstetrics and Gynecology, Assistant Professor (60336162)
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Project Period (FY) |
2006 – 2007
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Project Status |
Completed (Fiscal Year 2007)
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Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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Keywords | Endometriosis / Bacterial endotoxin / Peritoneal fluid / Menstrual blood / Escherichia coli / PGE2 / Complements C3 / C4 / TLR4 / Escherichia coli / 補体系 / Eschericia coli |
Research Abstract |
We demonstrated higher concentration of bacterial endotoxin in the peritoneal fluid and TLR4-mediated growth of endometriosis in our research experiment of 2006. We extended our research experiment in 2007 and examined the source of bacterial endotoxin in menstrual blood and peritoneal fluid of women with endometriosis. Escherichia coli(E.coli, strain K-12, serotype, 0111: B4)was cultured in LB(Laria-Bertani)agar plate and was treated with a variable concentration of PGE2 in culture. E.coli was detected in menstrual blood and this was significantly higher in women with endometriosis(10^5-10^7CFU/ml)than that in non-endometriosis(<10^2CFU/ml). As a cell wall extract of E.coli, we also detected higher concentration of endotoxin in the menstrual blood of women with endometriosis than that in non-endometriosis. A significantly increased growth of E.coli was observed in response to a wide range of PGE2 concentration(1pg/ml-100ng/ml)when compared with control(DMSO without PGE2).PGE2 level was
… More
also significantly higher in the menstrual blood of women with endometriosis than that in control women(negative control)or that in seminal fluid(positive control).Addition of PHA(1μg/ml-100g/ml) dose-dependently and significantly increased the growth of lymphocytes of both women with and without endometriosis. However, co-treatment with PGE2 significantly abrogated PHA-stimulated growth of lymphocytes. This growth suppressive effect of PGE2 on lymphocytes was only observed in women with endometriosis. The co-culture experiment with PHA-treated lymphocytes and culture media derived from either macrophages or stromal cells significantly suppressed the growth promoting effect of PHA and this effect was recovered after treatment with NS-398, a selective COX2 inhibitor. Lower complements C3/C4 levels were also found in the menstrual blood of women with endometriosis that may promote E.coli growth. Our results suggest that higher PGE2 levels in menstrual blood, a direct growth promoting or immunosuppressive effect of PGE2 and complement system could be responsible for the increased contamination of E.coli in the menstrual blood of women with endometriosis. These may be consequently involved in higher bacterial endotoxin levels in PF and TLR4-mediated growth of endometriosis. Less
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Report
(3 results)
Research Products
(70 results)
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[Journal Article] Multifunctional role of hepatocyte growth factor in the development of pelvic endometriosis2008
Author(s)
Khan, KN., Kitajima, M., Hiraki, K., Fujishita, A., Ishimaru, T., Sekine, I., Masuzaki, H
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Journal Title
WES e-journal(review article) (in press)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Immunopathogenesis of pelvic endometriosis : role of hepatocyte growth factor, macrophages and ovarian steroids2008
Author(s)
Khan, KN., Ishimaru, T., Kitajima, M., Hiraki, K., Fujishita, A., Sekine, I., Masuzaki, H
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Journal Title
Am J Reprod Immunol(review article) (in press)
NAID
Description
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[Journal Article] Toll-like receptor 4(TLR4)-mediated growth of endometriosis by human heat shock protein 702008
Author(s)
Khan, KN., Kitajima, M., Imamura, T., Hiraki, K., Fujishita, A., Sekine, I., Ishimaru, T., Masuzaki, H
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Journal Title
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[Journal Article] Re-evaluation of the indication and limitation of laparoscopic salpingotomy for tubal pregnancy2008
Author(s)
Fujishita, A., Khan, KN., Kitajima, M., Hiraki, K., Miura, S., Ishimaru, T., Masuzaki, H
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Journal Title
Euro J Obstet Gynecol Reprod Biol 37(2)
Pages: 210-216
NAID
Description
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[Journal Article] Toll-like receptors in innate immunity : role of bacterial endotoxin and toll-like receptor 4(TLR4)in endometrium, endometriosis and placenta2007
Author(s)
Khan, KN., Kitajima, M., Hiraki, K., Fujishita, A., Ishimaru, T., Masuzaki, H
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Journal Title
Inflammation and Immunity(review article in Japanese) 15
Pages: 56-68
Description
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[Journal Article] Higher prostaglandin E2 and lower complements C3/C4 levels in menstrual blood : a possible mechanism of Escherichia coli contamination in the menstrual blood of women with endometriosis2007
Author(s)
Khan, KN., Kitajima, M., Hiraki, K., Fujishita, A., Ishimaru, T., Sekine, I., Masuzaki, H
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Journal Title
Am J Reprod Immunol 57(5)
Pages: 323-324
Description
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[Journal Article] Role of bacterial endotoxin and endogenous heat shock protein 70(Hsp70)in pelvic inflammation and TLR4-meidated growth of endometriosis2007
Author(s)
Khan, KN., Kitajima, M., Hiraki, K., Fujishita, A., Ishimaru, T., Sekine, I., Masuzaki, H
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Journal Title
Am J Reprod Immunol 58(3)
Pages: 198-199
Description
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[Journal Article] Higher levels of hepatocyte growth factor in menstrual blood and peritoneal fluid : an association with the development of endometriosis2007
Author(s)
Khan, KN., Kitajima, M., Hiraki, K., Fujishita, A., Ishimaru, T., Sekine, I., Masuzaki, H
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Journal Title
Proceedings of the 20th Asian and Oceanic Congress of Obstetrics and Gynecology
Pages: 196-196
Description
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[Journal Article] Differential infiltration of macrophages and prostaglandin production by different uterine leiomyomas2006
Author(s)
Miura, S., Khan, KN., Kitajima, M., Hiraki, M., Shingo, M., Masuzaki, H., Samejima, T., Fujishita, A., Ishimaru, T
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Journal Title
Hum Reprod 21(10)
Pages: 2545-2554
NAID
Description
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[Presentation] Seminal Fluid Promotes the Growth of Endometriosis : Is Condom Use Necessary to Prevent the Development of Endometriosis?2008
Author(s)
Khan, KN., Kitajima, M., Hiraki, K., Fujishita, A., Sekine, I., Ishimaru, T., Masuzaki, H
Organizer
The 29th Endometriosis Research Meeting
Place of Presentation
Kochi
Description
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[Presentation] Prostaglandin E2 stimulates the growth of Escherichia coli : an association with E.coli contamination in menstrual blood, higher endotoxin level in peritoneal fluid and TLR4-mediated growth of endometriosis2008
Author(s)
Khan, KN., Kitajima, M., Hiraki, K., Fujishita, A., Katamine, S., Sekine, I., Ishimaru, T., Masuzaki, H
Organizer
Selected oral presentation at the 10th World Congress of Endometriosis(WCE)
Place of Presentation
Melbourne, Australia
Description
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[Presentation] Heat treatment of human serum promotes the growth of Escherichia coli : a possible involvement of complement system in the growth of endometriosis2008
Author(s)
Khan, KN., Kitajima, M., Hiraki, K., Fujishita, A., Katamine, S., Sekine, I., Ishimaru, T., Masuzaki, H
Organizer
Poster presentation at the 10th World Congress of Endometriosis(WCE)
Place of Presentation
Melbourne, Australia
Description
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[Presentation] Higher Prostaglandin E2 and lower complements C3/C4 levels in menstrual blood : a possible mechanismof Escherichia coli contamination in the menstrual blood of women with endometriosis2007
Author(s)
Khan, KN., Kitajima, M., Hiraki, K., Imamura, T., Fujishita, A., Sekine, I., Ishimaru, T., Masuzaki, H
Organizer
The 59th Japan Obstetrics & Gynecology Congress
Place of Presentation
Kyoto
Description
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[Presentation] Differential infiltration of macrophages and prostaglandin production by different uterine Ieiomyomas : a possible implication in myoma-associated infertility2007
Author(s)
Khan, KN., Miura, S., Kitajima, M., Hiraki, K., Moriyama, S., Samejima, T., Fujishita, A., Sekine, I., Ishimaru, T., Masuzaki, H
Organizer
Oral presentation at the 16th Annual Congress of International Society for Gynecologic Endoscopy(ISGE)
Place of Presentation
Osaka
Description
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[Presentation] Higher Prostaglandin E2 and lower complements C3/C4 levels in menstrual blood : a possible mechanism of Escherichia coli contamination in the menstrual blood of women with endometriosis2007
Author(s)
Khan, KN., Kitajima, M., Hiraki, K., Imamura, T., Fujishita, A., Sekine, I., Ishimaru, T., Masuzaki, H
Organizer
Oral presentation at the 27th Annual Meeting of American Society for Reproductive Immunology(ASRI)in Toronto
Place of Presentation
Canada
Description
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[Presentation] Role of bacterial endotoxin and endogenous heat shock protein 70(Hsp70)in pelvic inflammation and TLR4-mediated growth of endometriosis2007
Author(s)
Khan, KN., Kitajima, M., Hiraki, K., Imamura, T., Fujishita, A., Sekine, I., Ishimaru, T., Masuzaki, H
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Oral presented at the seminar session of The 5th European Congress of Reproductive Immunology(ECRI)
Place of Presentation
Berlin, Germany
Description
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[Presentation] Higher levels of hepatocyte growth factor In menstrual blood and peritoneal fluid : an Association with the development of pelvic endometriosis2007
Author(s)
Khan, KN., Kitajima, M., Hiraki, K., Imamura, T., Fujishita, A., Sekine, I., Ishimaru, T., Masuzaki, H
Organizer
Oral Presentation at the 20th Annual Meeting of Asian and Oceanic Congress of Obstetrics and Gynecology(AOCOG)
Place of Presentation
Tokyo
Description
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[Presentation] Bacterial endotoxin, toll-like receptor 4(TLR4)and macrophages : an association in the pathogenesis of endometriosis2006
Author(s)
Khan, KN., Kitajima, M., Hiraki, K., Moriyama, S., Yamaguchi, N., Katamine, S., Matsuyama, T., Sekine, I., Fujishita, A., Ishimaru, T., Masuzaki, H
Organizer
Paper presentation at Symposium session of the 51st Annual Meeting of the Japan Society for Reproductive Medicine(JSRM)
Place of Presentation
in Osaka
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[Presentation] Toll-like receptor 4-mediated growth of endometriosis by endogenous heat shock protein 702006
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Endo2006, The 88th Annual Meeting of American Endocrine Society
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[Presentation] Escherichia coli in menstrual blood : an association with bacterial endotoxin and toll-like receptor 4(TLR4)-mediated growth of endometriosis2006
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Paper presentation at the Symposium session of 3rd International Congress on Reproductive Immunobiology
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[Presentation] Escherichia coli in menstrual blood : an association with bacterial endotoxin and toll-like receptor 4(TLR4)mediated growth of endometriosis
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The 58th Japan Obstetrics & Gynecology Congress
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[Presentation] Interleukin-6 and tumor necrosis factor α-mediated expression of hepatocyte growth factor and its involvement in the growth of endometriosis
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The 58th Japan Obstetrics & Gynecology Congress
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[Presentation] Heat treatment of human serum promotes the growth of Escherichia coli : a possible involvement of complement system in the growth of endometriosis
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The 28th Endometriosis Research Meeting
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[Presentation] Prostaglandin E2 stimulates the growth of Escherichia coli : an association between PGE2 and E.coli contamination in the menstrual blood of women with endometriosis
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The 28th Endometriosis Research Meeting
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[Presentation] Changes in macrophage infiltration and micro-vessel density in endometriosis, adenomyosis and uterine myoma after GnRH agonist therapy
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