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选择性雌激素受体调节器的免疫活性是基因和巨细胞亚型特异的,但汇聚在Il1b下调调节上

Chiara Sfogliarini¹, Giovanna Pepe¹, Candida Maria Cesta²

¹Department of Pharmaceutical Sciences, University of Milan, 20133 Milan, Italy.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

|July 13, 2023

概括

选择性雌激素受体调节剂 (SERMs),如拉洛西芬,在巨细胞中表现出双重免疫活性. 这些药物,包括拉洛西芬,可以调节免疫基因表达和细胞因子的产生,这表明抗菌疗法的潜力.

科学领域:

免疫学免疫学免疫学
药理学药理学是指药理学的学科.
分子生物学分子生物学

背景情况:

选择性雌激素受体调节器 (SERMs) 用于与雌激素受体α (ERα) 相关的疾病.
目前正在探索SERM的ERα独立用途,包括抗微生物策略.
巨细胞的免疫反应对于对抗病原体至关重要,但SERM对巨细胞的影响尚不清楚.

研究的目的:

研究拉洛西芬和塔莫西芬对各种巨细胞亚型免疫基因表达的影响.
阐明参与巨细胞SERM活动的分子通路 (ERα,PI3K,NRF2).
在炎症条件下评估SERM对巨细胞反应的影响.

主要方法:

在小鼠和人类巨细胞 (腹,骨髓衍生,微质,血液衍生) 中比较拉洛西芬和塔莫西芬的活性.
测试免疫基因表达,包括Vegfa,Hmox1和Il1b.
研究了ERα,PI3K和NRF2通路的作用.
研究了对脂聚糖 (LPS) 的反应及其对TNFα和IL1β产生的影响.

主要成果:

拉洛西芬表现出双重活性:ERα对抗性和非目标效应.
微分子拉洛西芬通过皮质巨细胞中的PI3K/NRF2上调免疫代谢基因 (Vegfa,Hmox1).
在所有巨类型中,SERM 始终向下调节 Il1b mRNA,独立于 PI3K/NRF2.
在特定细胞亚型的情况下,SERM会增强LPS诱导的TNFα产生,并增加IL1β分泌.

结论:

拉洛西芬和其他SERM在巨细胞中具有复杂的免疫调节特性.
SERM激活特定的免疫通路 (PI3K/NRF2) 并影响细胞因子的产生.
巨体是利用SERM的抗菌能力的潜在治疗标.

关键词:

药物重新定位是药物重新定位.雌激素是一种雌激素.一个IL1ββ.感染感染感染巨细胞是一个巨细胞.拉洛西芬的使用方法这就是SERMs.塔莫西芬 (Tamoxifen) 是一种

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