Effects of cytokines on the pathogenesis of endometriosis and infertility associated with endometriosis

细胞因子对子宫内膜异位症发病机制及子宫内膜异位症相关不孕症的影响

• 批准号: 11470350
• 负责人: TERAKAWA Naoki
• 金额: $ 4.22万
• 依托单位: Tottori University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470350/
• 关键词: Endometriosis; Pathogenesis; Infertility; Endometriotic stromal cells; Peritoneal macrophages; Cytokines; IL-6; IL-8; 増殖・進展; TNFα; 間質細胞; TNF-α

Endometriosis, which occurs in 10% of reproductive aged women, is characterized by the presence and growth of endometrial-like tissue outside the uterus. The pathogenesis of endometriosis and its link to infertility is controversial. Peritoneal fluid in women with endometriosis contains an increased number of activated macrophages that secrete a variety of cytokines, including interleukin (IL)-6, IL-8 and tumor necrosis factor-α (TNFα). The purpose of this study is to investigate whether IL-6, IL-8 and TNFα are related to progress and infertility of this disease.Peritoneal fluid levels of IL-6, IL-8 and TNFα were significantly higher in patients with endometriosis compared with patients without endometriosis. The concentrations of these cytokines in patients with active endometriosis increased as the size and number of active lesions increased. Expressions of transcripts of IL-6 receptor, glycoprotein 130, IL-8 receptor and TNFα receptor were observed in both endometrial and endometrio … More tic stromal cells.Tumor necrosis factor-α increased the expression of IL-6 messenger RNA and protein in endometriotic cells in a dose-dependent manner. The addition of IL-6 inhibited the development of mouse 1-cell embryo to blastocyst in vitro. The percentage of motile spermatoza decreased by the addition of both IL-6 and soluble IL-6 receptor. These results suggested that IL-6 may relate to the infertility associated with endometriosis.Interleukin-6 had no effect on the growth of stromal cells in endometrial tissue from the proliferative phase. In contrast, the addition of IL-6 induced significant inhibition of stromal cells in tissue from the secretary phase. On the other hand, stromal cells of endometriotic tissues were resistant to IL-6, showing no inhibitory response. Interleukin-8 significantly increased the number of cells and DNA synthesis in the endometriotic stromal cells in a dose-dependent manner. Tumor necrosis factor-α induced the gene and protein expression of IL-8 in endometriotic stromal cells in a dose-dependent fashion. The addition of TNF α promoted the proliferation of the endometriotic stromal cells, and the stimulatory effects of TNF α were abolished by the adding anti-IL-8 antibody. These cytokines may associate with the progression of the disease.In conclusion, IL-6, IL-8 and TNF α may contribute to the pathogenesis of endometriosis and infertility associated with endometriosis. Less

子宫内膜异位症发生在10%的育龄妇女中，其特征在于子宫外的子宫样组织的存在和生长。子宫内膜异位症的发病机制及其与不孕症的联系是有争议的。子宫内膜异位症患者的腹腔液中含有大量活化的巨噬细胞，这些巨噬细胞分泌多种细胞因子，包括白细胞介素（IL）-6，IL-8和肿瘤坏死因子-α（TNFα）。子宫内膜异位症患者腹腔液中IL-6、IL-8和TNF α水平显著高于非子宫内膜异位症患者，IL-6、IL-8和TNFα水平与子宫内膜异位症的进展和不孕有关。活动性子宫内膜异位症患者中这些细胞因子的浓度随着活动性病变的大小和数量的增加而增加。IL-6受体、糖蛋白130、IL-8受体和TNFα受体在子宫内膜和子宫内膜组织中均有表达 ...更多信息 肿瘤坏死因子-α（TNF-α）呈剂量依赖性地增加增生细胞中IL-6 mRNA和蛋白的表达。IL-6对小鼠1-细胞胚胎体外发育有抑制作用。同时加入IL-6和可溶性IL-6受体均能降低精子活动率。提示IL-6可能与子宫内膜异位症不孕有关，IL-6对子宫内膜组织中增殖期基质细胞的生长无影响。相反，IL-6的加入诱导了组织中基质细胞从分泌期的显著抑制。另一方面，增生组织的基质细胞对IL-6具有抗性，没有显示出抑制反应。白细胞介素-8可显著增加骨髓基质细胞的细胞数和DNA合成，并呈剂量依赖性。肿瘤坏死因子-α可剂量依赖性地诱导增生间质细胞表达IL-8基因和蛋白。加入TNF α可促进骨髓基质细胞的增殖，加入抗IL-8抗体可消除TNF α的刺激作用。结论IL-6、IL-8和TNF α可能参与了子宫内膜异位症及不孕症的发病机制。少

项目成果

H.Yoshioka, T.Harada, T.Iwabe, Y.Nagano, F.Taniguchi, M.Tanikawa, N.Terakawa: "Menstrual cycle-specific inhibition of the proliferation of endometrial stromal cells by interleukin 6 and its soluble receptor."Am J Obstet Gynecol. 180(5). 1088-1094 (1999)

H.Yoshioka、T.Harada、T.Iwabe、Y.Nagano、F.Taniguchi、M.Tanikawa、N.Terakawa：“白细胞介素 6 及其可溶性受体对月经周期特异性抑制子宫内膜基质细胞的增殖。”

寺川直樹: "子宮内膜症とサイトカイン"日本産科婦人科学会雑誌. 52 8. 1202-1207 (2000)

Naoki Terakawa：“子宫内膜异位症和细胞因子”日本妇产科学会杂志 52 8. 1202-1207 (2000)。

T.Iwabe, T.Harada, T.Tsudo, Y.Nagano, S.Yoshida, M.Tanikawa, N.Terakawa: "Tumor necrosis factor-α promotes proliferation of endometriotic stromal cells by inducing interleukin-8 gene and protein expression."J Clin Endocrinol Metab. 85(2). 824-829 (2000)

T.Iwabe、T.Harada、T.Tsudo、Y.Nagano、S.Yoshida、M.Tanikawa、N.Terakawa：“肿瘤坏死因子-α 通过诱导白细胞介素 8 基因和蛋白表达来促进子宫内膜异位基质细胞的增殖。 “J Clin Endocrinol Metab. 85(2).824-829 (2000)

H.Yoshioka: "Menstrual cycle-specific inhibition of the proliferation of endometrial stromal cells by interleukin 6 and its solube receptor"Am.J.Obstet.Ginecol.. 188・5. 1088-1094 (1999)

H. Yoshioka：“白细胞介素 6 及其溶解受体对子宫内膜基质细胞增殖的月经周期特异性抑制”Am. J. Ginecol.. 188・5 (1999)。

T.Tsudo: "Altered gene expression and secretion of interleukin-6 in stromal cells derived from endometriotic tissues"Fertil.Steril.. 73・2. 205-211 (2000)

T.Tsudo：“子宫内膜异位组织来源的基质细胞中白细胞介素 6 的基因表达和分泌发生改变”Fertil.Steril.. 73·211 (2000)。