Role of cytokines in development of endometriosis

细胞因子在子宫内膜异位症发展中的作用

• 批准号: 10671540
• 负责人: HARADA Tasuku
• 金额: $ 2.11万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671540/
• 关键词: endometriosis; cytokine; MMP; TIMP; interleukin-6; interleukin-10; endometrium; IL-6 soluble receptor; インターロイキンー6; インターロイキンー10; ILー6可溶性受容体

We have measured peritoneal fluid (PF) levels of matrix metalloproteinase-9 (MMP-9), its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-10 (IL-10) in patients with endometriosis. Although the concentrations of MMP-9 was below the detectable level, high concentrations of TIMP-1 and IL-10 were present in the PF. The levels of IL-10 in PF was significantly higher in patients with endometriosis than in patients without endometriosis. In order to examine the effects of IL-6 or IL-10 on the gene expression of TIMP-1, endometrial and endometriotic stromal cells were collected from the uterus or from ovarian chocolate cysts. The stimulatory effects of these cytokines have been elucidated.We have conducted the study to investigate the possible role of IL-6, soluble IL-6 receptor in the growth of endometrial and endometriotic cells. We examined the effect of IL-6, soluble IL-6 receptor or combination of both factors on the proliferation of endometrial and endometriot … More ic stromal cells. IL-6 receptor had no effect on the growth of stromal cells in tissue from the proliferative phase. In contrast, the addition of 200 or 400pg/ml of IL-6 induced significant inhibition of cell proliferation. Similarly, the addition of soluble IL-6 receptor caused significant suppression in the growth of endometrial stromal cells in tissue from the secretory phase, but not the proliferative phase. On the other hand, stromal cells of endometriotic tissues were resistant to IL-6, showing no inhibitory response. Although the combination treatment did not affect the proliferation of stromal cells of proliferative phase and of endometriotic tissues, 10gn/ml of soluble IL-6 inhibited proliferation of stromal cells of the secretory phase in the presence of 1ng/ml of soluble IL-6 receptor. The expression of transcripts of IL-6 receptor and gp130 was observed in the endometrial cells from the proliferative and secretory phases and in endometriotic cells. IL-6 may play a central role in regulation of the growth of endometrial cells as a mediator of endocrine action. Endometriotic cells may behave differently from the normal counterpart in terms of the inhibitory regulation exerted by IL-6. Less

我们测量了子宫内膜异位症患者腹膜液 (PF) 中基质金属蛋白酶 9 (MMP-9)、其抑制剂、金属蛋白酶 1 组织抑制剂 (TIMP-1) 和白细胞介素 10 (IL-10) 的水平。尽管 MMP-9 的浓度低于可检测水平，但 PF 中存在高浓度的 TIMP-1 和 IL-10。子宫内膜异位症患者PF中IL-10的水平显着高于无子宫内膜异位症患者。为了检查IL-6或IL-10对TIMP-1基因表达的影响，从子宫或卵巢巧克力囊肿收集子宫内膜和子宫内膜异位基质细胞。这些细胞因子的刺激作用已被阐明。我们进行了这项研究来调查IL-6（可溶性IL-6受体）在子宫内膜和子宫内膜异位细胞生长中的可能作用。我们检查了 IL-6、可溶性 IL-6 受体或两种因子的组合对子宫内膜和子宫内膜基质细胞增殖的影响。 IL-6受体对增殖期组织中基质细胞的生长没有影响。相反，添加200或400pg/ml的IL-6引起细胞增殖的显着抑制。类似地，添加可溶性IL-6受体显着抑制分泌期组织中子宫内膜基质细胞的生长，但不抑制增殖期。另一方面，子宫内膜异位组织的基质细胞对IL-6有抵抗力，没有表现出抑制反应。虽然联合治疗不影响增殖期基质细胞和子宫内膜异位组织的增殖，但在1ng/ml可溶性IL-6受体存在下，10gn/ml可溶性IL-6抑制分泌期基质细胞的增殖。在增殖期和分泌期的子宫内膜细胞以及子宫内膜异位细胞中观察到IL-6受体和gp130转录本的表达。 IL-6 作为内分泌作用的介质，可能在子宫内膜细胞生长的调节中发挥核心作用。子宫内膜异位细胞在 IL-6 的抑制调节作用方面可能与正常细胞不同。较少的

项目成果

T. Harada, H. Yoshioka, et al.: "Increased interleukin-6 levels in peritoneal fluid of infertile patients with active endometriosis"Am. J. Obstet Gynecol.. 176. 593-597 (1997)

T. Harada、H. Yoshioka 等人：“患有活动性子宫内膜异位症的不孕患者腹膜液中白细胞介素 6 水平升高”Am。

H.Yoshioka, T.Harada, T.Iwabe, Y.Nagano, F.Taniguchi, M.Tanikawa, N.Terakawa.: "Menstral cycle-specific inhibition in the proliferation of endometrial stromal cells by interleukin-6 and its soluble receptor"Am J Obstete Gynecol. 180. 1088-94 (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

T.Iwabe: "Pathogenetic significance of increased levels of interleukin-8 in peritoneal fluid of patients with endometriosis." Fertil Steril. 69・5. 924-930 (1998)

T.Iwabe：“子宫内膜异位症患者腹腔液中白细胞介素 8 水平升高的病理学意义。”Fertil Steril 69·5 (1998)。

T.Harada, H.Yoshioka, S.Yoshida, T.Iwabe, Y.Onohara, M.Tanikawa, N.Terakawa.: "Increased interleukin-6 levels in peritoneal fluid of infertile patients with active endometriosis"Am J Obstet Gynecol. 176. 593-7 (1997)

T.Harada、H.Yoshioka、S.Yoshida、T.Iwabe、Y.Onohara、M.Tanikawa、N.Terakawa.：“活动性子宫内膜异位症不孕患者腹腔液中白细胞介素 6 水平升高”Am J Obstet Gynecol。

T.Tsudo, T.Harada, T.Iwabe, M.Tanikawa, Y.Nagano, F.Taniguchi, N.Terakawa.: "Altered gene expression and secretion of interleukin-6 in stromal cells derived from endometriotic tissues"Fertil Steril. 73. 205-211 (2000)

T.Tsudo、T.Harada、T.Iwabe、M.Tanikawa、Y.Nagano、F.Taniguchi、N.Terakawa.：“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。