Effect of GnRH analogues on apoptosis and release of interleukin-1β and vascular endothelial growth factor in endometrial cell cultures from patients with endometriosis
Effect of GnRH analogues on apoptosis and release of interleukin-1β and vascular endothelial growth factor in endometrial cell cultures from patients with endometriosis
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DOI：
10.1093/humrep/deg356
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发表时间：
2003-09-01
影响因子：
6.1
通讯作者：
Barañao, RI
中科院分区：
文献类型：
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作者：
Meresman, GF;Bilotas, MA;Barañao, RI
背景技术背景：本研究的目的是评价GnRH类似物对体外在位子宫内膜细胞凋亡及白细胞介素-1 β（IL-1 β）和血管内皮生长因子（VEGF）释放的影响。方法：对16例未经治疗的子宫内膜异位症患者和14例对照者的在位子宫内膜活检标本进行研究。在与作为GnRH激动剂的醋酸亮丙瑞林（LA）、作为GnRH拮抗剂的antide以及两者联合孵育后，在上皮子宫内膜细胞培养物中评价了细胞凋亡、IL-1 β和VEGF释放。采用吖啶橙-溴化乙锭技术检测凋亡细胞百分比，采用酶联免疫吸附测定（ELISA）试剂盒检测IL-1 β和VEGF浓度。研究结果：我们发现LA（100 ng/ml）可促进子宫内膜异位症患者和对照组子宫内膜细胞的凋亡，这种作用可被10（-7）mol/l antide逆转。在对照组和子宫内膜异位症患者的培养物中，LA下调了IL-1 β和VEGF的释放。加入10（-7）mol/l抗肽可逆转这种抑制作用。与基础条件相比，用antide（10-7 mol/l）处理的子宫内膜培养物未显示出任何显著影响。结论：GnRH激动剂似乎对子宫内膜细胞培养有直接影响，通过增加凋亡细胞的百分比和减少促有丝分裂细胞因子如IL-1 β和VEGF的释放。
BACKGROUND: The aim of the present study was to evaluate the effect of GnRH analogues on the in-vitro eutopic endometrial cell apoptosis and release of interleukin-1beta (IL-1beta) and vascular endothelial growth factor (VEGF). METHODS: Biopsy specimens of eutopic endometrium obtained from 16 women with untreated endometriosis and 14 controls were studied. Apoptosis, IL-1beta and VEGF release were evaluated in epithelial endometrial cell cultures after incubation with leuprolide acetate (LA) as GnRH agonist, antide as GnRH antagonist, and a combination of both. The percentage of apoptotic cells was evaluated by the acridine orange-ethidium bromide technique, and IL-1beta and VEGF concentrations were assessed by using commercial enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: We found that LA (100 ng/ml) enhanced apoptosis in endometrial cell cultures from endometriosis patients and controls and this effect was reversed by antide at 10(-7) mol/l. IL-1beta and VEGF release was down-regulated by LA in cultures from controls and endometriosis patients. The addition of antide 10(-7) mol/l reversed this inhibition. Endometrial cultures treated with antide at 10-7 mol/l did not show any significant effects compared with basal conditions. CONCLUSIONS: GnRH agonists appear to have a direct effect in endometrial cells cultures, by enhancing the percentage of apoptotic cells and decreasing the release of pro-mitogenic cytokines such as IL-1beta and VEGF.