Role of Bacterial Endotoxin and Innate Immune System in Endometriosis

细菌内毒素和先天免疫系统在子宫内膜异位症中的作用

• 批准号: 18591837
• 负责人: KHAN Khaleque
• 金额: $ 2.49万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591837/
• 关键词: Endometriosis; Bacterial endotoxin; Peritoneal fluid; Menstrual blood; Escherichia coli; PGE2; Complements C3; C4; TLR4; Escherichia coli; 補体系; Eschericia coli

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

我们在2006年的研究实验中证实了腹膜液中细菌内毒素浓度升高以及tlr4介导的子宫内膜异位症的生长。我们在2007年扩展了我们的研究实验，检查了子宫内膜异位症妇女经血和腹膜液中细菌内毒素的来源。大肠杆菌(E。大肠杆菌，菌株K-12，血清型，0111:B4)在LB（Laria-Bertani）琼脂平板上培养，用不同浓度的PGE2处理，在经血中检测到大肠杆菌，子宫内膜异位症妇女的经血中检测到大肠杆菌（10^5-10^7CFU/ml）明显高于非子宫内膜异位症妇女（<10^2CFU/ml）。作为大肠杆菌的细胞壁提取物，我们也检测到子宫内膜异位症女性月经血中的内毒素浓度高于非子宫内膜异位症女性。与对照组（不含PGE2的DMSO）相比，在PGE2浓度范围内（1pg/ml-100ng/ml），大肠杆菌的生长显著增加。子宫内膜异位症患者经血中PGE2水平也明显高于对照组（阴性对照组）或精液中PGE2水平（阳性对照组）。PHA（1μg/ml-100g/ml）的添加量呈剂量依赖性，显著增加了子宫内膜异位症患者和非子宫内膜异位症患者淋巴细胞的生长。然而，与PGE2共同治疗可显著消除pha刺激的淋巴细胞生长。PGE2对淋巴细胞的生长抑制作用仅在子宫内膜异位症患者中观察到。PHA处理过的淋巴细胞与巨噬细胞或基质细胞培养基共培养实验显著抑制了PHA的促生长作用，经选择性COX2抑制剂NS-398处理后，这种作用得以恢复。在患有子宫内膜异位症的女性的经血中也发现了较低的补体C3/C4水平，这可能促进大肠杆菌的生长。我们的研究结果表明，经血中较高的PGE2水平，PGE2和补体系统的直接生长促进或免疫抑制作用可能是导致子宫内膜异位症女性经血中大肠杆菌污染增加的原因。因此，这些可能与PF和tlr4介导的子宫内膜异位症生长中较高的细菌内毒素水平有关。少

项目成果

月経血中の大腸菌(Escherichia Coli)および腹水中のエンドトキシンは骨盤内炎症およびToll-like receptor4を介した子宮内膜症の増殖に関与する

经血中的大肠杆菌和腹水中的内毒素参与盆腔炎症和Toll样受体4介导的子宫内膜异位症的生长。

• 发表时间: 2006
• 作者: Khan;KN.;Kitajima;M.;Hiraki;K.;Imamura;T.;Fujishita;A.;Sekine;I.;Ishimaru;T.;Masuzaki;H;Khan KN;カレクネワズカーン
• 通讯作者: カレクネワズカーン

Re-evaluation of the Indication and Limitation of Laparoscopic Salpingotomy for Tubal Pregnancy.

重新评估腹腔镜输卵管切开术治疗输卵管妊娠的适应症和局限性。

• 发表时间: 2008
• 期刊: Eur J Obstet Gynecol Reprod Biol (in press)
• 作者: Fujishita;A.;Khan;KN.;Kitajima;M.;Hiraki;K.;Miura;S.;Ishimaru;T.;Masuzaki;H;Khan KN;Fujishita A
• 通讯作者: Fujishita A

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 endometriosis

经血中较高的前列腺素E2和较低的补体C3/C4水平：子宫内膜异位症女性经血中大肠杆菌污染的可能机制

• 发表时间: 2007
• 作者: Khan;KN.;Kitajima;M.;Hiraki;K.;Imamura;T.;Fujishita;A.;Sekine;I.;Ishimaru;T.;Masuzaki;H
• 通讯作者: H

Higher Prostaglandin E2 and lower complements C3/C4levels in menstrual blood:apossible mechanism of Escherichia coli contamination in the menstrual blood of women with endometriosis

经血中较高的前列腺素E2和较低的补体C3/C4水平:子宫内膜异位症妇女经血中大肠杆菌污染的可能机制

• 发表时间: 2007
• 作者: Khan;KN.;Kitajima;M.;Hiraki;K.;Fujishita;A.;Sekine;I.;Ishimaru;T.;Masuzaki;H;Khan KN;Khan KN;カレクネワズカーン;Khan KN;Khan KN
• 通讯作者: Khan KN

Role of bacterial endotoxin and endogenous heat shock protein 70(Hsp70)in pelvic inflammation and TLR4-mediated growth of endometriosis

细菌内毒素和内源性热休克蛋白70(Hsp70)在盆腔炎症和TLR4介导的子宫内膜异位症生长中的作用

• 发表时间: 2007
• 作者: Khan;KN.;Kitajima;M.;Hiraki;K.;Imamura;T.;Fujishita;A.;Sekine;I.;Ishimaru;T.;Masuzaki;H
• 通讯作者: H