核受体Nurr1优先表达在人类的亲炎性巨细胞中,并限制了它们的炎症特征
Miguel A Solís-Barbosa1, Eduardo Santana1, José R Muñoz-Torres1
1Department of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), 07360 Mexico City, Mexico.
International immunology
|December 9, 2023
概括
Nurr1核受体表达与亲炎性人类巨细胞有关. 激活Nurr1可以降低炎症媒介的产生,这表明它起到抑制炎症的作用.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 核受体1 (核受体子家族4A组) 调节炎症.
- 人类巨细胞中Nurr1的作用尚不清楚.
- 巨细胞对于调节炎症反应至关重要.
研究的目的:
- 研究人类巨细胞中Nurr1的表达和活性.
- 确定Nurr1在巨细胞两极分化和炎症媒介产生的作用.
- 探索Nurr1抗炎作用的机制.
主要方法:
- 人类单细胞分化为使用GM-CSF和M-CSF的亲和抗炎性巨细胞.
- 使用激素C-DIM12和IP7e的Nurr1激活.
- 分析炎症基因表达,细胞因子产生和NF-κB通路活性.
- 检查Nurr1在皮肤巨细胞从型皮虫患者.
主要成果:
- 在预炎性巨细胞中,Nurr1的表达更高.
- 激活Nurr1降低了多种炎症媒介 (TNF,IL-1β,IL-6,IL-8,IL-12p40,CCL2,IFN-β,ROS) 的产生.
- Nurr1 缺乏增加了炎症基因表达.
- Nurr1与NF-κB p65相互作用,C-DIM12稳定了该复合体,减少了NF-κB的活动.
- 在TNF产生的皮肤巨细胞中发现了高Nurr1水平,这些巨细胞存在于雄性皮虫病变中.
结论:
- 在人类巨细胞中,Nurr1表达与亲炎性表型相关.
- 激活Nurr1减弱了炎症媒介的合成.
- Nurr1可能会作为巨细胞驱动炎症的负调节剂.
- 在炎症性疾病中,Nurr1是潜在的治疗点.
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