SR-16234是一种独特的选择性雌激素受体调节剂,它通过抑制子宫内膜异位基质细胞的核因子-kappa B通路来抑制其增殖和疼痛相关因子的表达。

IF 2.5 3区 医学 Q3 IMMUNOLOGY American Journal of Reproductive Immunology Pub Date : 2024-10-30 DOI:10.1111/aji.70010
Emiko Yamane, Yukihiro Azuma, Mei Matsumoto, Eri Sato, Yoshiaki Ota, Tasuku Harada, Fuminori Taniguchi
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引用次数: 0

摘要

问题:SR-16234(SR)是一种选择性雌激素受体(ER)调节剂,它对人类子宫内膜异位基质细胞(ESC)有什么影响?从21名接受腹腔镜手术治疗卵巢子宫内膜异位症(OEs)的患者身上获取子宫内膜组织。从 18 名无子宫内膜异位症的患者身上获取黄体期的正常异位子宫内膜。用SR培养从OEs和正常异位子宫内膜基质细胞(NESCs)中分离出来的ESCs,然后将其暴露于肿瘤坏死因子(TNF)-α。培养 48 小时后,用 WST-8 试验评估了 SR 对细胞增殖的影响。实时 RT-PCR 评估了炎症和疼痛相关因子的基因表达,包括白细胞介素 (IL)-6、IL-8、环氧化酶 (COX)-2、瞬时受体位点类香草素 (TRPV)1、ESR1 和 ESR2。蛋白印迹分析评估了抑制因子κBα(IκBα)、细胞外信号调节激酶(ERK)1/2 和蛋白激酶 B(AKT)的磷酸化情况。通过酶联免疫吸附分析评估了ILs、前列腺素(PG)E2和核内p65的合成:结果:SR处理可抑制TNF-α诱导的ESCs增殖20%,但不能抑制NESCs。SR还降低了ESCs中IL-6、IL-8、COX-2、TRPV1、ESR1和ESR2 mRNA的表达以及ILs蛋白和PGE2的合成,而在NESCs中仅降低了TRPV1 mRNA的表达。与仅添加 TNF-α 相比,SR 可抑制 TNF-α 诱导的磷酸化 IκBα 水平约 50%,核内 p65 蛋白减少 30%。然而,SR 并不影响 AKT 和 ERK1/2 的磷酸化:SR通过抑制核因子-kappa B通路抑制炎症和疼痛相关因子的表达,似乎是子宫内膜异位症的潜在治疗药物。
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SR-16234, a Unique Selective Estrogen Receptor Modulator, Suppressed Proliferation and Pain-Related Factor Expression by Inhibition of the Nuclear Factor-kappa B Pathway in Endometriotic Stromal Cells

Problem

What is the effect of SR-16234 (SR), a selective estrogen receptor (ER) modulator, on human endometriotic stromal cells (ESCs)?

Method of Study

Endometriotic tissues were obtained from 21 patients undergoing laparoscopic surgery for ovarian endometriomas (OEs). Normal eutopic endometrium during the luteal phase was obtained from 18 patients without endometriosis. ESCs isolated from OEs and normal eutopic endometrial stromal cells (NESCs) were cultured with SR and subsequently exposed to tumor necrosis factor (TNF)-α. After 48 h of incubation, the effect of SR on cell proliferation was evaluated by the WST-8 assay. The gene expressions of inflammatory and pain-related factors, including interleukin (IL)-6, IL-8, cyclooxygenase (COX)-2, transient receptor potential vanilloid (TRPV)1, ESR1, and ESR2, were evaluated by real-time RT-PCR. The phosphorylation of Inhibitor κBα (IκBα), extracellular signal-regulated kinase (ERK)1/2, and Protein Kinase B (AKT) were evaluated by western blot analysis. ILs, prostaglandin (PG) E2, and intranuclear p65 syntheses were assessed by ELISA.

Results

SR treatment repressed TNF-α-induced proliferation by 20% in ESCs but not NESCs. SR also reduced IL-6, IL-8, COX-2, TRPV1, ESR1, and ESR2 mRNA expressions and ILs protein, and PGE2 synthesis in ESCs, whereas in NESCs, only TRPV1 mRNA expression was decreased. SR suppressed TNF-α-induced phosphorylated IκBα levels by approximately 50%, and intranuclear p65 protein was reduced by 30% compared to addition of only TNF-α in ESCs. However, SR did not affect the phosphorylation of AKT and ERK1/2.

Conclusions

SR appears to be a potential therapeutic agent for endometriosis by suppressing inflammatory and pain-related factor expressions by inhibiting the nuclear factor-kappa B pathway.

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来源期刊
CiteScore
6.20
自引率
5.60%
发文量
314
审稿时长
2 months
期刊介绍: The American Journal of Reproductive Immunology is an international journal devoted to the presentation of current information in all areas relating to Reproductive Immunology. The journal is directed toward both the basic scientist and the clinician, covering the whole process of reproduction as affected by immunological processes. The journal covers a variety of subspecialty topics, including fertility immunology, pregnancy immunology, immunogenetics, mucosal immunology, immunocontraception, endometriosis, abortion, tumor immunology of the reproductive tract, autoantibodies, infectious disease of the reproductive tract, and technical news.
期刊最新文献
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