白细胞介素 (IL)-1β、肿瘤坏死因子 (TNF)-α 和干扰素-γ 对人子宫内膜基质细胞体外产生上皮中性粒细胞激活肽-78 (ENA-78)、IL-8 和 IL-6 的剂量反应效应。

Dose-response effect of interleukin (IL)-1β, tumour necrosis factor (TNF)-α, and interferon-γ on the in vitro production of epithelial neutrophil activating peptide-78 (ENA-78), IL-8, and IL-6 by human endometrial stromal cells.

机构信息

Department of Obstetrics and Gynaecology, University of Berne, Berne, Switzerland.

出版信息

Arch Gynecol Obstet. 2011 Jun;283(6):1291-6. doi: 10.1007/s00404-010-1520-3. Epub 2010 May 27.

DOI:10.1007/s00404-010-1520-3

PMID:20505949

Abstract

PURPOSE

The production of epithelial neutrophil activating peptide-78 (NA-78) and the interleukins IL-8 and IL-6 by endometrial stromal cells is stimulated by pro-inflammatory interleukin-1 (IL-1) and tumour necrosis factor-α (TNF-α). IL-8 is suggested to play a role in the pathogenesis of endometriosis, and in these women the peritoneal fluid concentrations of ENA-78 and IL-8 are increased. TNF-α has been tested together with interferon-γ because of their cooperative stimulation of IL-6. The release of IL-8, however, is inhibited with increasing interferon levels. The aim of the study was the analysis of the production of ENA-78, IL-6 and IL-8 by cultured human endometrial stromal cells in the presence of varying concentrations of IL-1β, TNF-α, and interferon-γ.

METHODS

Eutopic endometrial tissue was obtained from seven cycling, endometriosis-free women undergoing laparoscopy for reasons of infertility or pain. The release of ENA-78, IL-8 and IL-6 by the isolated and monolayer cultured stromal cell fraction in the presence of IL-1β (0.08 to 50 ng/mL), TNF-α, and interferon-γ (both 20 to 500 ng/mL) was determined.

RESULTS

IL-1β stimulated the production of IL-8, IL-6, and ENA-78 dose dependently from 0.08 to 2.0 ng/mL (ENA-78) or to 10 ng/mL (IL-8, IL-6); at 50 ng/mL a decrease in release was observed for IL-8 and IL-6. TNF-α stimulation yielded a plateau between 20 and 100 ng/mL. Interferon-γ stimulated IL-6 and inhibited IL-8 production above 20 ng/mL. ENA-78 release was largely unaffected by interferon-γ.

CONCLUSIONS

IL-1β and TNF-α stimulate stromal cytokine production cumulatively with different dose-response curves. The presence of interferon-γ has opposite effects on IL-8 and IL-6. TNF-α and interferon-γ should be investigated separately in future in vitro studies with endometrial cells and explants.

摘要

目的

子宫内膜基质细胞产生上皮中性粒细胞激活肽-78（NA-78）和白细胞介素-8（IL-8）和白细胞介素-6（IL-6）受到促炎白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNF-α）的刺激。IL-8 被认为在子宫内膜异位症的发病机制中起作用，在这些女性中，腹腔液中 ENA-78 和 IL-8 的浓度增加。由于它们协同刺激 IL-6，因此已经测试了 TNF-α 与干扰素-γ 一起使用。随着干扰素水平的升高，IL-8 的释放受到抑制。本研究的目的是分析不同浓度的白细胞介素-1β（IL-1β）、TNF-α 和干扰素-γ（两者均为 20 至 500 ng/mL）存在下培养的人子宫内膜基质细胞中 ENA-78、IL-6 和 IL-8 的产生。

方法

从因不孕或疼痛而接受腹腔镜检查的 7 名月经周期正常、无子宫内膜异位症的女性中获得正常子宫内膜组织。在 0.08 至 50 ng/mL 的 IL-1β、TNF-α 和干扰素-γ（均为 20 至 500 ng/mL）存在下，分离并单层培养基质细胞部分，测定 ENA-78、IL-8 和 IL-6 的释放。

结果

IL-1β 以 0.08 至 2.0 ng/mL（ENA-78）或 10 ng/mL（IL-8、IL-6）的剂量依赖性刺激 IL-8、IL-6 和 ENA-78 的产生；在 50 ng/mL 时，IL-8 和 IL-6 的释放减少。TNF-α 刺激在 20 至 100 ng/mL 之间产生平台。干扰素-γ 刺激 IL-6 的产生并抑制 20 ng/mL 以上的 IL-8 产生。干扰素-γ 对 ENA-78 的释放影响不大。